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Targeted gene disruption of Hsp70-2 results in failed meiosis, germ cell apoptosis, and male infertility.
Open accessAbstract
In addition to the five 70-kDa heat shock proteins (HSP70) common to germ cells and somatic tissues of mammals, spermatogenic cells synthesize HSP70-2 during meiosis. To determine if this unique stress protein has a critical role in meiosis, we used gene-targeting techniques to disrupt Hsp70-2 in mice. Male mice homozygous for the mutant allele (Hsp70-2 -/-) did not synthesize HSP70-2, lacked postmeiotic spermatids and mature sperm, and were infertile. However, neither meiosis nor fertility was affected in female Hsp70-2 -/- mice. We previously found that HSP70-2 is associated with synaptonemal complexes in the nucleus of meiotic spermatocytes from mice and hamsters. While synaptonemal complexes assembled in Hsp70-2 -/- spermatocytes, structural abnormalities became apparent in these cells by late prophase, and development rarely progressed to the meiotic divisions. Furthermore, analysis of nuclei and genomic DNA indicated that the failure of meiosis in Hsp70-2 -/- mice was coincident with a dramatic increase in spermatocyte apoptosis. These results suggest that HSP70-2 participates in synaptonemal complex function during meiosis in male germ cells and is linked to mechanisms that inhibit apoptosis.
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Citations
Cited by
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Hormonal and genetic control of germ cell apoptosis in the testis
HIKIM, A. P. S. (1999) · Reviews of Reproduction · doi:10.1530/revreprod/4.1.38 · Cited by 482
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Grad, I., & Picard, D. (2007) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2007.05.018 · Cited by 423
Bromodomain‐dependent stage‐specific male genome programming by Brdt
Gaucher, J., Boussouar, F., Montellier, E., Curtet, S., Buchou, T., Bertrand, S., Hery, P., Jounier, S., Depaux, A., Vitte, A., et al. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.233 · Cited by 253
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Metadata
- Authors
- Dix, D. J., Allen, J. W., Collins, B. W., Mori, C., Nakamura, N., Poorman-Allen, P., Goulding, E. H., & Eddy, E. M.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1996-04-16
- Volume
- 93
- Issue
- 8
- Pages
- 3264-3268
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1981048926
- Cited by
- 540
- References
- 0
- FWCI
- 31.68
- Type
- journal article
- Language
- en
- Open access
- green
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- Dix, D. J., Allen, J. W., Collins, B. W., Mori, C., Nakamura, N., Poorman-Allen, P., Goulding, E. H., & Eddy, E. M. (1996). Targeted gene disruption of Hsp70-2 results in failed meiosis, germ cell apoptosis, and male infertility. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.93.8.3264
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