Robertsonian chromosomes and the nuclear architecture of mouse meiotic prophase spermatocytes
© Berrios et al.; licensee BioMed Central Ltd. 2014
Received: 18 April 2014
Accepted: 21 April 2014
Published: 14 May 2014
The nuclear architecture of meiotic prophase spermatocytes is based on higher-order patterns of spatial associations among chromosomal domains from different bivalents. The meiotic nuclear architecture depends on the chromosome characteristics and consequently is prone to modification by chromosomal rearrangements. In this work, we consider Mus domesticus spermatocytes with diploid chromosome number 2n = 40, all telocentric, and investigate a possible modification of the ancestral nuclear architecture due to the emergence of derived Rb chromosomes, which may be present in the homozygous or heterozygous condition.
In the 2n = 40 spermatocyte nuclei random associations mediated by pericentromeric heterochromatin among the 19 telocentric bivalents ocurr at the nuclear periphery. The observed frequency of associations among them, made distinguishable by specific probes and FISH, seems to be the same for pairs that may or may not form Rb chromosomes. In the homozygote Rb 2n = 24 spermatocytes, associations also mediated by pericentromeric heterochromatin occur mainly between the three telocentric or the eight metacentric bivalents themselves. In heterozygote Rb 2n = 32 spermatocytes all heterochromatin is localized at the nuclear periphery, yet associations are mainly observed among the three telocentric bivalents and between the asynaptic axes of the trivalents.
The Rb chromosomes pose sharp restrictions for interactions in the 2n = 24 and 2n = 32 spermatocytes, as compared to the ample possibilities for interactions between bivalents in the 2n = 40 spermatocytes. Undoubtedly the emergence of Rb chromosomes changes the ancestral nuclear architecture of 2n = 40 spermatocytes since they establish new types of interactions among chromosomal domains, particularly through centromeric and heterochromatic regions at the nuclear periphery among telocentric and at the nuclear center among Rb metacentric ones.
During the meiotic prophase of spermatocytes, chromosomes form a distinctive arrangement in the nuclear space, governed mainly by the synapses between homologous chromosomes that form bivalents and by the union of their ends to the nuclear envelope [1–3]. The bivalent configuration generates a meiotic nuclear architecture dependent on the chromosome characteristics [4–6]. Consequently, this architecture is subject to modification by chromosomal rearrangements.
In this work, we investigate how the ancestral nuclear architecture of Mus domesticus spermatocytes with a diploid chromosome number 2n = 40, all of them telocentric, is modified by the emergence of derived Rb metacentric chromosomes, which may be present in the homozygous or heterozygous condition.
Synapsis between homologous chromosomes is a process that culminates with the formation of the synaptonemal complex (SC). The SC is a tripartite proteinaceous scaffold consisting of two lateral elements (homologous chromosome axes) and a medial component that stabilizes the joint between the homologous chromosomes forming the bivalents [7–10].
Numerous proteins are involved in the SC structure. SYCP3 protein is the main constituent of the axis of each homologous chromosome, and SYCP1 protein is located between the axes of homologous chromosomes, binding them together in synapsis with transverse filaments [11, 12]. Both ends of each bivalent SC are attached to the nuclear envelope, so that each SC forms an arc of different extension depending on the length of the synapsed chromosomes. The chromatin, organized in loops, is connected to the lateral elements of the SC, hence the chromatin domains are sequentially ordered along each bivalent SC. Finally, the SC’trajectory determines the place for the chromosomal domains to occupy within the nuclear space. This is not trivial, because interactions or associations among heterologous chromosomal domains depend on the real possibility of establishing contacts between them together with their structural and functional affinities that could favor the consolidation of such interactions.
In this regard, the spermatocytes of Mus domesticus 2n = 40 containing 19 autosomal telocentric bivalents with abundant pericentromeric heterochromatin near their proximal ends naturally favor the associations among them over the nuclear envelope . Comparative analysis of the observed combinations of associated and non-associated bivalents in the spermatocytes, and the predictions of an ad-hoc developed probabilistic model for associations between indistinguishable elements, suggest that these associations could indeed take place randomly . Notice that associations are not a phenomenon unique to meiotic prophase cells. They have also been described in Mus somatic cells with highly complex chromocenters, involving several chromosomes and the nucleoli .
Large blocks of satellite DNA (pericentromeric heterochromatin) surround the centromere and extend towards the proximal end of each chromosome, thus favoring the occurrence of Rb translocations in Mus. Double-strand breaks of DNA with nearly identical base components, in addition to physical proximity, facilitates the fusion of different chromosomes . Rb translocations involve double-strand DNA breaking at the centromere level in two telocentric (acrocentric) chromosomes, followed by a repair (fusion) that binds the respective long arms, creating a metacentric Rb chromosome. The short arms (p) of the original telocentric chromosomes, including the proximal telomeres, part of the satellite DNA, and generally one centromere, are all lost. However, this loss of DNA does not significantly alter the total amount of DNA as compared with the standard Mus karyotype . Rb translocation is the most common chromosomal rearrangement in mammals  and represents the type of chromosomal change that most effectively contributes to differentiation or speciation of natural populations .
In Mus, Rb translocations have resulted in more than 40 different chromosomal races (or subspecies), ranging from 2n = 40 to 2n = 22. These chromosomal races are natural populations characterized by altogether about 100 Rbs chromosomes with different combinations of arms , many of which emerged and spread extremely rapidly within populations of the standard karyotype .
Metacentric Rb chromosomes can become numerous in the Mus genome, leading to a reduction of ancestral telocentric chromosomes and to an emergence of new mixed karyotypes. Furthermore, crossing between wild homozygotes 2n = 40 and Rb homozygotes produce F1 hybrids in whose genomes the ancestral telocentric chromosomes are reunited with the metacentric derivatives. Trivalents are formed in the meiotic prophase spermatocytes of these mice, in which a metacentric chromosome is synapsed with the long arms of two telocentric chromosomes. Varying degrees of synapses are established among the proximal ends of the involved telocentric chromosomes, despite being heterologous .
The presence of Robertsonian (Rb) metacentric chromosomes, which can be multiple in this species, constitutes a valuable opportunity to study how these new chromosomes modify the original, ancestral nuclear architecture built just for telocentric bivalents.
To this end, we studied the meiotic nuclear organization of:
Homozygote 2n = 24 spermatocytes, with 8 pairs of metacentric Rb chromosomes, 3 pairs of telocentric chromosomes, and the XY sex pair.
Heterozygote 2n = 32 spermatocytes, with 8 Rb metacentric chromosomes, 22 telocentric chromosomes, and the XY pair.
We further compared both families of spermatocytes with the nuclear architecture of the ancestral homozygote 2n = 40.
We found different patterns of nuclear architecture according to chromosome constitution of the spermatocytes. The Rb chromosomes present in 2n = 24 and 2n = 32 spermatocytes drastically restrict the possibilities for interaction between the heterochromatic domains as compared with the wealth of random associations observed in 2n = 40 spermatocytes.
Early prophase and the chromosome nuclear distribution in 2n = 40 and 2n = 24 spermatocytes
When the early prophase nuclei were treated with DAPI that stains DNA rich in AT sequences, which in Mus is the DNA that underlies the pericentromeric heterochromatin, the 2n = 40 spermatocyte nucleus showed one large DAPI-positive chromocenter whose location matched the regions of aggregated centromere. The 2n = 24 spermatocytes showed at least two DAPI-positive chromocenters, one at the nuclear periphery and the other toward the center of the nucleus. We showed previously that the initial aggregation of centromeres occurring in lepto-zygotene of 2n = 40 spermatocytes will eventually resolve into several smaller aggregates that we can observe in pachytene or more advanced stages of meiotic prophase .
Bivalent configuration and associations in 2n = 40 pachytene spermatocytes
Frequency of 2n = 40 spermatocyte bearers with two given distinguished bivalents associated between them
Pair of distinguishable bivalents
Spermatocyte percentage with those bivalents associated between them
16 and 17
9 and 14
14 and 16
9 and 17
Bivalent configuration and associations in 2n = 24 pachytene spermatocytes
Combination of associated and single metacentric/telocentric bivalents per nucleus observed in 2n = 24 spermatocytes
Combinations between 8 metacentric bivalents
Combinations between 3 telocentric bivalents
Number of spermatocytes per nuclear combination
% of spermatocytes per Class
- - -
3(3); 9(2-1); 1(1-1-1)
2(3); 3(2-1); 1(1-1-1)
2(3); 4(2-1); 2(1-1-1)
1(3); 4(2-1); 2(1-1-1)
3(3); 4(2-1); 3(1-1-1)
4(3); 8(2-1); 2(1-1-1)
27(3); 56(2-1); 17(1-1-1)
Trivalent configurations in spermatocyte nuclei of heterozygotes 2n = 32
Number of partially asynapsed trivalents and the type of ectopic asociations in 2n = 32 heterocygote spermatocytes
The nuclear architecture of spermatocytes in meiotic prophase is primarily determined by the synaptic organization of the bivalents, bound by their telomeres to the nuclear envelope and describing arc-shaped trajectories through the nuclear space. However, over this basic meiotic organization, the spermatocyte nuclear architecture is also conditioned by the individual characteristics of the chromosomes and the opportunity for interactions between their domains. The homogeneity in the morphology of the chromosomes of Mus domesticus 2n = 40, in addition to the numerous subspecies with reduced diploid numbers and carriers of metacentric Rb chromosomes, makes this species a convenient model to evaluate the above proposal. In this sense, the comparative analysis of the nuclear architecture of Mus spermatocytes with different chromosomal constitutions (2n = 40, 2n = 24 and 2n = 32) allowed us to establish which differences in nuclear organization are attributable to Rb chromosomes.
Moreover, all telocentric chromosomes of Mus 2n = 40 exhibit abundant pericentromeric heterochromatin that is composed of two distinct repetitive DNA sequences, the minor and major satellites. It has been shown that the major satellites with the heterochromatin protein 1alpha form clusters, creating an association of several bivalents . Previous analyses have allowed us to demonstrate that associations between autosomal bivalents mediated by heterochromatin are very frequent and can be considered as being random . In this work, in which two bivalents were distinguishable each time, we found that the frequency of association between them was close to 10%, coinciding with the expected rate if associations were at random. There were no significant differences in the frequency of association by spermatocyte between chromosome pairs that form Rb chromosomes (9/14 and 16/17) versus those that do not (9/16 and 14/17), nor did we find higher frequencies of association between bivalents 16 and 17 that are nucleolar and whose NOR regions are both near the pericentromeric heterochromatin. Ribosomal gene expression occurs in pachytene spermatocytes; this situation may have contributed to the association of NORs from different bivalents in the production of a common nucleolus, as has been described in somatic and meiotic cells [5, 13]. However, as Mus has multiple nucleolar chromosomes, we cannot rule out preferential associations among other nucleolar chromosomes . In any case, frequent random associations among all bivalents would be consistent with the necessary physical proximity among their heterochromatic regions for Rb fusions to occur among any of the 19 bivalents, as has been described for the different subspecies of Mus. On the other hand, the homology of satDNA sequences shared by the mouse telocentric chromosomes  might have occurred by means of multiple small exchanges among these large tracts of tandemly repeated DNA . The associations among the autosomal bivalents during meiotic prophase, precisely through their heterochromatic domains, would also provide a scenario in which these frequent recombinational exchanges between non-homologous chromosomes may have occurred. A similar origin has been proposed for the concerted evolution of the ribosomal DNA spacers on non-homologous nucleolar chromosomes [24–26].
In many organisms, a meiosis-specific organization of chromosomes called the “bouquet configuration,” which is a clustering of telomeres on the inner nuclear envelope, appears to facilitate homologous recognition and alignment by concentrating all chromosomes within a limited region of the nuclear volume [27–30]. In the bouquet of the 2n = 40 spermatocytes, all of the heterochromatic ends of the telocentric chromosomes cluster together, forming a large chromocenter. Later, the progress of the prophase increases the nuclear volume and the movement of telomeres over the nuclear envelope, and consequently the great original chromocenter breaks down into the smaller chromocenters seen in the pachytene stage . In contrast, during the bouquet of 2n = 24 spermatocytes, it was remarkable, that only two chromocenters were observed, a small one at the nuclear periphery and another with abundant heterochromatin toward the center of the nucleus. Therefore, two different areas for association are characteristic for these nuclei: one among the heterochromatins of telocentric bivalents, and another among the heterochromatins of metacentric bivalents. This organization continues toward the pachytene stage, where most of the spermatocytes show the telocentric bivalents tightly associated among themselves and the metacentric bivalents associated in a looser way forming two or more groups. We suggest that this new nuclear architecture would favor the progressive fusion of the remaining telocentric chromosomes. It is also possible that this narrowing of association opportunities is related to the overall trend toward production of metacentric chromosomes, as observed in the chromosomal evolution of this species [16, 31]. On the other hand, association between the heterochromatic regions of the metacentric bivalents is the scenario in which WARTS may occur. In these Rb rearrangements, described also in the karyotypes of Mus, two Rb metacentric chromosomes exchange their arms due to breakage and reciprocal fusion at the pericentric heterochromatin level of both [32, 33]. The described topological nuclear organization allows for the repeated encounter between chromosomal domains that may eventually experience rearrangements among them. However, under this topographic scenario it is also necessary to consider that during meiotic prophase, a programmed induction of DNA double-strand breaks (DSBs) leads to the exchange of genetic material between homologous chromosomes . DSBs preferentially occurs at discrete sites called hotspots whose localization seems to be influenced by both local chromatin and higher-order chromosome structures . It is not known if hotspots are preferentially localized at the heterochromatic domains of the Mus spermatocytes. However, on these meiotic prophase nuclei the full DNA repair machinery would be available, which could account for an exchange between heterologous DNA that may change the structure of the involved chromosomes.
In heterozygote 2n = 32 spermatocytes, another nuclear architecture emerges, which in this case accounts for the meeting of two different chromosome complements, one from 2n = 40 homozygotes and the other from 2n = 24 homozygotes. These hybrids, or similar, may occur naturally in any overlapping area of two subpopulations of Mus, one bearing the ancestral karyotype and other that has diverged by the presence of multiple Rb chromosomes. In Rb heterozygote spermatocytes, recognition and synapsis between the two parental chromosome complements occur, forming eight trivalents, three telocentric bivalents, and a sexual bivalent, similar to what has been previously described for other Rb hybrids of Mus. Each trivalent has three points of attachment to the nuclear envelope, two corresponding to the distal telomeres and the third to the heterologous proximal ends of the telocentric chromosomes. This organization leads to the three centromeres clustering together at the nuclear periphery. Depending on the distance between the distal and proximal telomeres the trivalents may take different configurations at the nuclear space. The ultimate reason why telomeres move away or why the trivalents present different configurations remains unknown. On the other hand, in any of these configurations, the centromeric and heterochromatic domains of the very same eight pairs of telocentric chromosomes are always together in every trivalent and spermatocyte. This repeated convergence of the same pairs of heterochromatic domains should be also decisive in favoring the formation of new metacentric Rb chromosomes.
It has been reported that approximately 80% of the heterozygote spermatocytes in early prophase shows 2 to 6 trivalents with varying degrees of asynapsis between the short arms of telocentric chromosomes . Chromatin surrounding these areas of asynapsis experiences changes in condensation and modifications on the underlying proteins resulting in transcriptional repression. This entire phenomenon is known as MSUC for “Meiotic Silencing of Asynapsed Chromatin” . Some of the asynapsed trivalents were only connected between them or with the XY bivalent through this kind of chromatin. It has been reported that MSUC also delay the progress of meiotic prophase, which gives the opportunity that these chromosomal regions reach the synapsis what apparently it happens in many of the spermatocytes . Despite of this, we observed that in 68% of mid pachytene nuclei, the single axes of partially asynapsed trivalents established ectopic associations amongst themselves (15,7%), with the XY bivalent (27,1%) or both (23,6%). Furthermore, the presence of SCP1 protein between the heterologous axes demonstrates the formation of the SC medial element and thus the possibility of recombination between heterologous chromosomal regions, which can later lead to segregational problems between those chromosomes. Therefore, the configuration of trivalents and the relationships among their unsynaptic axes impact globally the architecture of the heterozygote pachytene nuclei and possibly may have consequences for the survival of the spermatocytes. Thus, ectopic bonds could be quite deleterious to the normal progress of prophase and also to the subsequent segregation of the involved chromosomes. Spermatocytes carrying these ectopic joints may be eliminated by apoptosis in prophase or metaphase I, a phenomenon that has been observed in the Rb heterozygote male germ line [38, 39]. All of these situations could explain the reduced fertility found in Rb hybrids [38, 40–42].
Clearly, the multiple presence of Rb metacentric chromosomes in 2n = 24 spermatocytes, as in the 2n = 32 heterozygotes, determines a new organization and distribution of chromosomal domains in the meiotic prophase nucleus and consequently changes the possibilities for interchromosomal relationships as compared to those present in the 2n = 40 spermatocytes. The nuclear architecture can achieve a new optimum as have been seen in homozygote spermatocytes 2n = 24. However, in heterozygote nuclei, the areas for meeting and interaction between chromosomal domains, which actually define the nuclear architecture, are unclear and their emerging trials rather seem to produce additional instability.
On the other hand, the significant changes in the spermatocyte nuclear architecture described here allow us to better understand the difficulties that a new Rb chromosomes face in surviving meiosis, and therefore to be inherited by the progeny and propagated into the reproductive community.
The Rb chromosomes pose sharp restrictions for interactions in the 2n = 24 and 2n = 32 spermatocytes, as compared to the ample possibilities for interactions between bivalents in the 2n = 40 spermatocytes.
The emergence of Rb chromosomes changes the ancestral nuclear architecture of 2n = 40 spermatocytes since they establish new types of interactions among chromosomal domains.
The associations are produced through centromeric and heterochromatic regions at the nuclear periphery among telocentric bivalents and at the nuclear center among Rb metacentric ones.
We analyzed spermatocytes from four male three-month-old Mus domesticus 2n = 40 CD1 mice with all telocentric chromosomes; spermatocytes from four males of the Milano II 2n = 24 with eight pairs of homozygote Rb metacentric chromosomes; and spermatocytes from four heterozygote Rb mice 2n = 32 with eight single Rb metacentric chromosomes. The heterozygote mice were generated by mating females of the laboratory strain CD1 2n = 40 and males of the Milano II race. Male and female specimens from the original natural populations were donated to our laboratory, by Drs Carlo Redi and Silvia Garagna from the Pavia University, Italy, as part of a collaborative research proyect.
The Rb chromosomes were the following: Rb (2.12), Rb (3.4), Rb (5.15), Rb (6.7), Rb (8.11), Rb (9.14), Rb (10.13), Rb (16.17). Numbers are according the 2n = 40 standard karyotype.
Mice were maintained at 22°C with a light/dark cycle of 12/12 hours and fed ad libitum. Procedures involving the use of the mice were reviewed and approved by the Ethics Committee of the Faculty of Medicine, Universidad de Chile and by the Ethics Committee of the Chilean National Science Foundation FONDECYT-CONICYT.
Spermatocyte squashes with 3-D preserved nuclei
Spermatocyte squashes that preserved the nuclear volume were obtained following the procedure described by Page et al. . Testes were removed and fixed in 2% formaldehyde in PBS containing 0.05% Triton X-100. Pieces of tubules were placed in a drop of fixing solution on a slide. They were gently minced with tweezers, and then a coverslip was added. Exerting pressure on the coverslip squashed the cells. The slides were frozen in liquid nitrogen, and coverslips were then removed.
Spermatocyte nuclear spreads
Spermatocyte spreads were obtained following the procedure described by Peters et al. . Briefly, a testicular cell suspension in 100 mM sucrose was spread onto a slide dipped in 1% paraformaldehyde in distilled water containing 0.15% Triton X-100 then left to dry for two hours in a moist chamber. The slides were subsequently washed with 0.08% Photoflo (Kodak), air-dried, and rehydrated in PBS.
Immunochemical identification of bivalents
The slides were incubated for 45 minutes at 37°C in a moist chamber with the primary antibodies: rabbit anti-SYCP3 1:100 (Abcam, ab15093); mouse anti-CENPA 1:200 (Abcam, ab13939); rabbit anti-H3K9me3 1:200 (Abcam ab8580); or mouse anti-phospho-histone H2AX (Ser139) 1:1000 clone JBW301 (Upstate, 05–636). Then, the slides were incubated for 30 minutes at room temperature with the secondary antibodies: FITC-conjugated goat anti-mouse IgG (1:50) (Sigma), or Texas red-conjugated goat anti rabbit IgG (1:200) (Jackson). Slides were counterstained with 1 μg/ml DAPI (4,6-diamidino-2-phenylindole). Finally, slides were rinsed in PBS and mounted in Vectashield (Vector).
In situ hybridization
In the microspreads of the 2n = 40 spermatocytes, chromosomes 9, 14, 16, or 17 were identified by in situ hybridization using commercial probes (MetaSystems). The slides were treated for 5 minutes in 1XPBS, dehydrated in a series of 70, 80, 90, and 100% ethanol for 2 minutes each, and air-dried at room temperature. The slides with the samples and the DNA probe were denatured together at 75°C for 2 minutes. Then, the slides were incubated in a humid chamber at 41°C for 16 hours. Next, the coverslip was removed, and the slides were washed in: 0.4X SSC at 72°C for 2 minutes; 2XSSC with 0.05% Tween20 at room temperature for 30 seconds, and twice in 1× PBS for 5 minutes each. Nuclear contrast was performed with DAPI, and coverslips were mounted with Vectashield.
Observations were made using a Nikon (Tokyo, Japan) Optiphot or Olympus BX61 microscope equipped with epifluorescence optics, and the images were photographed on a DS camera control unit DS-L1 Nikon or captured with an Olympus DP70 digital camera. All images were processed using Adobe Photoshop CS5.1 software or the public domain software ImageJ (National Institutes of Health, United States; http://rsb.info.nih.gov/ij).
FONDECYT Project #1120160, Chile, and BFU 2009/10987 del Ministerio de Ciencia e Innovación, España, supported this work.
- Zickler D, Kleckner N: Meiotic chromosomes: integrating structure and function. Annu Rev Genet 1999, 33: 603-754. 10.1146/annurev.genet.33.1.603View ArticlePubMedGoogle Scholar
- Page SL, Hawley RS: The genetics and molecular biology of the synaptonemal complex. Annu Rev Cell Dev Biol 2004, 20: 525-558. 10.1146/annurev.cellbio.19.111301.155141View ArticlePubMedGoogle Scholar
- Cohen PE, Pollack SE, Pollard JW: Genetic analysis of chromosome pairing, recombination, and cell cycle control during first meiotic prophase in mammals. Endocr Rev 2006, 27(4):398-426. 10.1210/er.2005-0017View ArticlePubMedGoogle Scholar
- Berrios S, Fernández-Donoso R, Ayarza E, Paulos A, Moreno M: Non-random distribution of the pericentromeric heterochromatin in meiotic prophase nuclei of mammalian spermatocytes. Genetica 1999, 106: 187-195. 10.1023/A:1003958712698View ArticlePubMedGoogle Scholar
- Berrios S, Fernández-Donoso R, Pincheira J, Page J, Manterola M, Cerda MC: Number and nuclear localisation of nucleoli in mammalian spermatocytes. Genetica 2004, 121(3):219-228.View ArticlePubMedGoogle Scholar
- Berrios S, Manterola M, Prieto Z, López-Fenner J, Page J, Fernández-Donoso R: Model of chromosome associations in Mus domesticus spermatocytes. Biol Res 2010, 43(3):275-285.View ArticlePubMedGoogle Scholar
- Heyting C: Synaptonemal complexes: structure and function. Curr Opin Cell Biol 1996, 8: 389-396. 10.1016/S0955-0674(96)80015-9View ArticlePubMedGoogle Scholar
- Von Wettstein D, Rasmussen SW, Holm PB: The synaptonemal complex in genetic segregation. Annu Rev Genet 1984, 18: 331-413. 10.1146/annurev.ge.18.120184.001555View ArticlePubMedGoogle Scholar
- Yang F, Wang PJ: The mammalian synaptonemal complex: a scaffold and beyond. Genome Dyn 2009, 5: 69-80.View ArticlePubMedGoogle Scholar
- Fraune J, Schramm S, Alsheimer M, Benavente R: The mammalian synaptonemal complex: protein components, assembly and role in meiotic recombination. Exp Cell Res 2012, 318(12):1340-1346. 10.1016/j.yexcr.2012.02.018View ArticlePubMedGoogle Scholar
- Lammers JHM, Offenberg HH, Van Aalderen M, Vink ACG, Dietrich AJJ, Heyting C: The gene encoding a major component of the lateral elements of synaptonemal complexes of the rat is related to X-linked lymphocyte-regulated genes. Mol Cell Biol 1994, 14: 1137-1146.PubMed CentralView ArticlePubMedGoogle Scholar
- Offenberg HH, Schalk JA, Rl M, Van Aalderen M, Kester HA, Dietrich AJ, Heyting C: SCP2: a major protein component of the axial elements of synaptonemal complexes of the rat. Nucleic Acids Res 1998, 26: 2572-2579. 10.1093/nar/26.11.2572PubMed CentralView ArticlePubMedGoogle Scholar
- Cerda M, Berrios S, Fernández-Donoso R, Garagna S, Redi C: Organization of complex nuclear domains in somatic mouse cells. Biol Cell 1999, 91: 55-65. 10.1111/j.1768-322X.1999.tb01084.xView ArticlePubMedGoogle Scholar
- Tsujimoto Y, Gorham J, Cossman J, Jaffe E, Croce C: The t(14;18) chromosome translocations involved in B-cell neoplasms result from mistakes in VDJ joining. Science 1985, 229: 1390-1393. 10.1126/science.3929382View ArticlePubMedGoogle Scholar
- Comings DE, Avelino E: DNA loss during Robertsonian fusion in studies of the tobacco mouse. Nat New Biol 1972, 237(76):199. 10.1038/newbio237199a0View ArticlePubMedGoogle Scholar
- King M: Species Evolution: The Role of Chromosome Change. Cambridge, U.K.: Cambridge Univ. Press; 1993.Google Scholar
- Garagna S, Marziliano N, Zuccotti M, Searle JB, Capanna E, Redi CA: Pericentromeric organization at the fusion point of mouse Robertsonian translocation chromosomes. Proc Natl Acad Sci U S A 2001, 98(1):171-175. 10.1073/pnas.98.1.171PubMed CentralView ArticlePubMedGoogle Scholar
- Redi C, Capanna E: Robertsonian heterozygotes in the house mouse and the fate of their germ cells. New York, New York: AlanR. Liss Inc; 1988.Google Scholar
- Britton-Davidian J, Catalan JDA Graca Ramalhinho M, Ganem G, Auffray JC, Capela R, Biscoito M, Searle JB, Da Luz Mathias M: Rapid chromosomal evolution in island mice. Nature 2000, 403: 158. 10.1038/35003116View ArticlePubMedGoogle Scholar
- Manterola M, Page J, Vasco C, Berríos S, Parra MT, Viera A, Rufas JS, Zuccotti M, Garagna S, Fernández-Donoso R: A high incidence of meiotic silencing of asynapsed chromatin is not associated with substantial pachytene loss in heterozygous male mice carrying multiple simple robertsonian translocations. PLoS Genet 2009, 5(8):e1000625. Epub 2009 Aug 28 10.1371/journal.pgen.1000625PubMed CentralView ArticlePubMedGoogle Scholar
- Guenatri M, Bailly D, Maison C, Almouzni G: Mouse centric and pericentric satellite repeats form distinct functional heterochromatin. J Cell Biol 2004, 166: 493-505. 10.1083/jcb.200403109PubMed CentralView ArticlePubMedGoogle Scholar
- Rowe LB, Janaswami PM, Barter ME, Birkenmeier EH: Genetic mapping of 18S ribosomal RNA-related loci to mouse chromosomes 5, 6, 9, 12, 17, 18, 19, and X. Mamm Genome 1996, 7(12):886-889. 10.1007/s003359900262View ArticlePubMedGoogle Scholar
- Kalitsis P, Griffiths B, Choo KH: Mouse telocentric sequences reveal a high rate of homogenization and possible role in Robertsonian translocation. Proc Natl Acad Sci U S A 2006, 103(23):8786-8791. 10.1073/pnas.0600250103PubMed CentralView ArticlePubMedGoogle Scholar
- Arnheim N, Krystal M, Schmickel R, Wilson G, Ryder O, Zimmer E: Molecular evidence for genetic exchanges among ribosomal genes on nonhomologous chromosomes in man and apes. Proc Natl Acad Sci U S A 1980, 77(12):7323-7327. 10.1073/pnas.77.12.7323PubMed CentralView ArticlePubMedGoogle Scholar
- Gonzalez IL, Sylvester JE: Human rDNA: evolutionary patterns within the genes and tandem arrays derived from multiple chromosomes. Genomics 2001, 73(3):255-263. 10.1006/geno.2001.6540View ArticlePubMedGoogle Scholar
- Eickbush TH, Eickbush DG: Finely orchestrated movements: evolution of the ribosomal RNA genes. Genetics 2007, 175(2):477-485. 10.1534/genetics.107.071399PubMed CentralView ArticlePubMedGoogle Scholar
- Scherthan H, Weich S, Schwegler H, Heyting C, Harle M, Cremer T: Centromere and telomere movements during early meiotic prophase of mouse and man are associated with the onset of chromosome pairing. J Cell Biol 1996, 134(5):1109-1125. 10.1083/jcb.134.5.1109View ArticlePubMedGoogle Scholar
- Scherthan H: A bouquet makes ends meet. Nat Rev Mol Cell Biol 2001, 2: 621-627. 10.1038/35085086View ArticlePubMedGoogle Scholar
- Carlton PM, Cande WZ: Telomeres act autonomously in maize to organize the meiotic bouquet from semipolarized chromosome orientation. J Cell Biol 2002, 157(2):231-242. 10.1083/jcb.200110126PubMed CentralView ArticlePubMedGoogle Scholar
- Harper L, Golubovskaya I, Cande WZ: A bouquet of chromosomes. J Cell Sci 2004, 117: 4025-4032. 10.1242/jcs.01363View ArticlePubMedGoogle Scholar
- Searle JB: Speciation, chromosomes, and genomes. Genome Res 1998, 8(1):1-3.PubMedGoogle Scholar
- Capanna E, Redi CA: Whole-arm reciprocal translocation (WART) between Robertsonian chromosomes: finding of a Robertsonian heterozygous mouse with karyotype derived through WARTs. Chromosome Res 1995, 3(2):135-137. 10.1007/BF00710676View ArticlePubMedGoogle Scholar
- Solano E, Castiglia R, Corti M: A new chromosomal race of the house mouse, Mus musculus domesticus, in the Vulcano Island-Aeolian Archipelago, Italy. Hereditas 2007, 144(3):75-77. 10.1111/j.2007.0018-0661.01988.xView ArticlePubMedGoogle Scholar
- Baudat F, Imai Y, de Massy B: Meiotic recombination in mammals: localization and regulation. Nat Rev Genet 2013, 14(11):794-806. 10.1038/nrg3573View ArticlePubMedGoogle Scholar
- Yamada T, Ohta K: Initiation of meiotic recombination in chromatin structure. J Biochem 2013, 154(2):107-114. 10.1093/jb/mvt054View ArticlePubMedGoogle Scholar
- Grao P, Coll MD, Ponsà M, Egozcue J: Trivalent behavior during prophase I in male mice heterozygous for three Robertsonian translocations: an electron-microscopic study. Cytogenet Cell Genet 1989, 152(3–4):105-110.View ArticleGoogle Scholar
- Mahadevaiah SK, Costa Y, Turner JM: Using RNA FISH to study gene expression during mammalian meiosis. Methods Mol Biol 2009, 558: 433-444. Review 10.1007/978-1-60761-103-5_25View ArticlePubMedGoogle Scholar
- Wallace BM, Searle JB, Everett CA: The effect of multiple simple Robertsonian heterozygosity on chromosome pairing and fertility of wild-stock house mice (Mus musculus domesticus). Cytogenet Genome Res 2002, 96(1-4):276-286. 10.1159/000063054View ArticlePubMedGoogle Scholar
- Oka A, Mita A, Takada Y, Koseki H, Shiroishi T: Reproductive isolation in hybrid mice due to spermatogenesis defects at three meiotic stages. Genetics 2010, 186(1):339-351. Epub 2010 Jul 6 10.1534/genetics.110.118976PubMed CentralView ArticlePubMedGoogle Scholar
- Redi CA, Garagna S, Hilscher B, Winking H: The effects of some Robertsonian chromosome combinations on the seminiferous epithelium of the mouse. J Embryol Exp Morphol 1985, 85: 1-19.PubMedGoogle Scholar
- Hauffe HC, Searle JB: Chromosomal heterozygosity and fertility in house mice (Mus musculus domesticus) from Northern Italy. Genetics 1998, 150(3):1143-1154.PubMed CentralPubMedGoogle Scholar
- Garagna S, Zuccotti M, Thornhill A, Fernandez-Donoso R, Berrios S, Capanna E, Redi CA: Alteration of nuclear architecture in male germ cells of chromosomally derived subfertile mice. J Cell Sci 2001, 114(Pt 24):4429-4434.PubMedGoogle Scholar
- Page J, Suja JA, Jl S, Rufas JS: Squash procedure for protein immunolocalization in meiotic cells. Chromosom Res 1998, 6: 639-664. 10.1023/A:1009209628300View ArticleGoogle Scholar
- Peters AH, Plug AW, Van Vugt MJ, De Boer P: A drying-down technique for the spreading of mammalian meiocytes from the male and female germline. Chromosome Res 1997, 5: 66-68. 10.1023/A:1018445520117View ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.