Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1995 Oct 24;92(22):10403–10407. doi: 10.1073/pnas.92.22.10403

Y chromosome short arm-Sxr recombination in XSxr/Y males causes deletion of Rbm and XY female sex reversal.

S H Laval 1, P H Glenister 1, C Rasberry 1, C E Thornton 1, S K Mahadevaiah 1, H J Cooke 1, P S Burgoyne 1, B M Cattanach 1
PMCID: PMC40805  PMID: 7479793

Abstract

We earlier described three lines of sex-reversed XY female mice deleted for sequences believed close to the testes-determining gene (Sry) on the Y chromosome short arm (Yp). The original sex-reversed females appeared among the offspring of XY males that carried the Yp duplication Sxr on their X chromosome. Earlier cytogenetic observations had suggested that the deletions resulted from asymmetrical meiotic recombination between the Y and the homologous Sxr region, but no direct evidence for this hypothesis was available. We have now analyzed the offspring of XSxr/Y males carrying an evolutionarily divergent Mus musculus domesticus Y chromosome, which permits detection and characterization of such recombination events. This analysis has enabled the derivation of a recombination map of Yp and Sxr, also demonstrating the orientation of Yp with respect to the Y centromere. The mapping data have established that Rbm, the murine homologue of a gene family cloned from the human Y chromosome, lies between Sry and the centromere. Analysis of two additional XY female lines shows that asymmetrical Yp-Sxr recombination leading to XY female sex reversal results in deletion of Rbm sequences. The deletions bring Sry closer to Y centromere, consistent with the hypothesis that position-effect inactivation of Sry is the basis for the sex reversal.

Full text

PDF

Images in this article

10404Fig. 1
on p.10404
10405Fig. 2
on p.10405
10405Fig. 4
on p.10405
10406Fig. 5
on p.10406
10407Fig. 6
on p.10407

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Affara N. A., Lau Y. F., Briggs H., Davey P., Jones M. H., Khwaja O., Mitchell M., Sargent C. Report and abstracts of the First International Workshop on Y Chromosome Mapping 1994. Cambridge, England, April 2-5, 1994. Cytogenet Cell Genet. 1994;67(4):359–402. doi: 10.1159/000133871. [DOI] [PubMed] [Google Scholar]
  2. Agulnik A. I., Mitchell M. J., Lerner J. L., Woods D. R., Bishop C. E. A mouse Y chromosome gene encoded by a region essential for spermatogenesis and expression of male-specific minor histocompatibility antigens. Hum Mol Genet. 1994 Jun;3(6):873–878. doi: 10.1093/hmg/3.6.873. [DOI] [PubMed] [Google Scholar]
  3. Ashworth A., Swift S., Affara N. Sequence of cDNA for murine Zfy-1, a candidate for Tdy. Nucleic Acids Res. 1989 Apr 11;17(7):2864–2864. doi: 10.1093/nar/17.7.2864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bishop C. E., Hatat D. Molecular cloning and sequence analysis of a mouse Y chromosome RNA transcript expressed in the testis. Nucleic Acids Res. 1987 Apr 10;15(7):2959–2969. doi: 10.1093/nar/15.7.2959. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bishop C. E., Weith A., Mattei M. G., Roberts C. Molecular aspects of sex determination in mice: an alternative model for the origin of the Sxr region. Philos Trans R Soc Lond B Biol Sci. 1988 Dec 1;322(1208):119–124. doi: 10.1098/rstb.1988.0119. [DOI] [PubMed] [Google Scholar]
  6. Burgoyne P. S., Mahadevaiah S. K., Sutcliffe M. J., Palmer S. J. Fertility in mice requires X-Y pairing and a Y-chromosomal "spermiogenesis" gene mapping to the long arm. Cell. 1992 Oct 30;71(3):391–398. doi: 10.1016/0092-8674(92)90509-b. [DOI] [PubMed] [Google Scholar]
  7. Capel B., Rasberry C., Dyson J., Bishop C. E., Simpson E., Vivian N., Lovell-Badge R., Rastan S., Cattanach B. M. Deletion of Y chromosome sequences located outside the testis determining region can cause XY female sex reversal. Nat Genet. 1993 Nov;5(3):301–307. doi: 10.1038/ng1193-301. [DOI] [PubMed] [Google Scholar]
  8. Capel B., Swain A., Nicolis S., Hacker A., Walter M., Koopman P., Goodfellow P., Lovell-Badge R. Circular transcripts of the testis-determining gene Sry in adult mouse testis. Cell. 1993 Jun 4;73(5):1019–1030. doi: 10.1016/0092-8674(93)90279-y. [DOI] [PubMed] [Google Scholar]
  9. Cattanach B. M., Evans E. P., Burtenshaw M. D., Barlow J. Male, female and intersex development in mice of identical chromosome constitution. Nature. 1982 Dec 2;300(5891):445–446. doi: 10.1038/300445a0. [DOI] [PubMed] [Google Scholar]
  10. Cattanach B. M., Pollard C. E., Hawker S. G. Sex-reversed mice: XX and XO males. Cytogenetics. 1971;10(5):318–337. doi: 10.1159/000130151. [DOI] [PubMed] [Google Scholar]
  11. Cattanach B. M., Rasberry C., Burtenshaw M. D., Evans E. P. Illegitimate pairing of the X and Y chromosomes in Sxr mice. Genet Res. 1990 Oct-Dec;56(2-3):121–128. doi: 10.1017/s0016672300035199. [DOI] [PubMed] [Google Scholar]
  12. Chandley A. C., Cooke H. J. Human male fertility--Y-linked genes and spermatogenesis. Hum Mol Genet. 1994;3(Spec No):1449–1452. doi: 10.1093/hmg/3.suppl_1.1449. [DOI] [PubMed] [Google Scholar]
  13. Coward P., Nagai K., Chen D., Thomas H. D., Nagamine C. M., Lau Y. F. Polymorphism of a CAG trinucleotide repeat within Sry correlates with B6.YDom sex reversal. Nat Genet. 1994 Mar;6(3):245–250. doi: 10.1038/ng0394-245. [DOI] [PubMed] [Google Scholar]
  14. Evans E. P., Burtenshaw M. D., Cattanach B. M. Meitoic crossing-over between the X and Y chromosomes of male mice carrying the sex-reversing (Sxr) factor. Nature. 1982 Dec 2;300(5891):443–445. doi: 10.1038/300443a0. [DOI] [PubMed] [Google Scholar]
  15. Ma K., Inglis J. D., Sharkey A., Bickmore W. A., Hill R. E., Prosser E. J., Speed R. M., Thomson E. J., Jobling M., Taylor K. A Y chromosome gene family with RNA-binding protein homology: candidates for the azoospermia factor AZF controlling human spermatogenesis. Cell. 1993 Dec 31;75(7):1287–1295. doi: 10.1016/0092-8674(93)90616-x. [DOI] [PubMed] [Google Scholar]
  16. McElreavy K., Vilain E., Abbas N., Costa J. M., Souleyreau N., Kucheria K., Boucekkine C., Thibaud E., Brauner R., Flamant F. XY sex reversal associated with a deletion 5' to the SRY "HMG box" in the testis-determining region. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):11016–11020. doi: 10.1073/pnas.89.22.11016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. McLaren A., Monk M. Fertile females produced by inactivation of an X chromosome of "sex-reversed' mice. Nature. 1982 Dec 2;300(5891):446–448. doi: 10.1038/300446a0. [DOI] [PubMed] [Google Scholar]
  18. McLaren A., Simpson E., Epplen J. T., Studer R., Koopman P., Evans E. P., Burgoyne P. S. Location of the genes controlling H-Y antigen expression and testis determination on the mouse Y chromosome. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6442–6445. doi: 10.1073/pnas.85.17.6442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. McLaren A., Simpson E., Tomonari K., Chandler P., Hogg H. Male sexual differentiation in mice lacking H-Y antigen. Nature. 1984 Dec 6;312(5994):552–555. doi: 10.1038/312552a0. [DOI] [PubMed] [Google Scholar]
  20. Mitchell M. J., Bishop C. E. A structural analysis of the Sxr region of the mouse Y chromosome. Genomics. 1992 Jan;12(1):26–34. doi: 10.1016/0888-7543(92)90402-e. [DOI] [PubMed] [Google Scholar]
  21. Roberts C., Weith A., Passage E., Michot J. L., Mattei M. G., Bishop C. E. Molecular and cytogenetic evidence for the location of Tdy and Hya on the mouse Y chromosome short arm. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6446–6449. doi: 10.1073/pnas.85.17.6446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Simpson E. M., Page D. C. An interstitial deletion in mouse Y chromosomal DNA created a transcribed Zfy fusion gene. Genomics. 1991 Nov;11(3):601–608. doi: 10.1016/0888-7543(91)90067-o. [DOI] [PubMed] [Google Scholar]
  23. Tease C., Cattanach B. M. Sex chromosome pairing patterns in male mice of novel Sxr genotypes. Chromosoma. 1989 Mar;97(5):390–395. doi: 10.1007/BF00292766. [DOI] [PubMed] [Google Scholar]
  24. Wang K., Koop B. F., Hood L. A simple method using T4 DNA polymerase to clone polymerase chain reaction products. Biotechniques. 1994 Aug;17(2):236–238. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES