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PMID:8622925

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Citation

Dix, DJ, Allen, JW, Collins, BW, Mori, C, Nakamura, N, Poorman-Allen, P, Goulding, EH and Eddy, EM (1996) Targeted gene disruption of Hsp70-2 results in failed meiosis, germ cell apoptosis, and male infertility. Proc. Natl. Acad. Sci. U.S.A. 93:3264-8

Abstract

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.

Links

PubMed PMC39594

Keywords

Animals; Apoptosis/genetics; Apoptosis/physiology; Cricetinae; Female; Gene Targeting; HSP70 Heat-Shock Proteins/genetics; HSP70 Heat-Shock Proteins/physiology; Infertility, Male/genetics; Infertility, Male/pathology; Infertility, Male/physiopathology; Male; Meiosis/genetics; Meiosis/physiology; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Knockout; Pregnancy; Spermatocytes/metabolism; Spermatocytes/pathology; Spermatogenesis/genetics; Spermatogenesis/physiology; Synaptonemal Complex/genetics; Testis/pathology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:HSP72

located_in

GO:0000795: synaptonemal complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:HSP72

involved_in

GO:0007286: spermatid development

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:HSP72

involved_in

GO:0007140: male meiotic nuclear division

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

MOUSE:HSP72

acts_upstream_of_or_within

GO:0007286: spermatid development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2447605

P

Seeded From UniProt

complete

MOUSE:HSP72

acts_upstream_of_or_within

GO:0007140: male meiotic nuclear division

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2447605

P

Seeded From UniProt

complete

MOUSE:HSP72

part_of

GO:0000795: synaptonemal complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

See also

References

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