Testicular degeneration in Bclw-deficient mice.
To identify genes required for mammalian spermatogenesis, we screened lines of mutant mice created using a retroviral gene-trap system for male infertility. Homozygous ROSA41 male mice exhibit sterility associated with progressive testicular degeneration. Germ-cell defects are first observed at 19 days post-natal (p19). Spermatogenesis is blocked during late spermiogenesis in young adults. Gradual depletion of all stages of germ cells results in a Sertoli-cell-only phenotype by approximately six months of age. Subsequently, almost all Sertoli cells are lost from the seminiferous tubules and the Leydig cell population is reduced. Molecular analysis indicates that the gene mutated is Bclw, a death-protecting member of the Bcl2 family. The mutant allele of Bclw in ROSA41 does not produce a Bclw polypeptide. Expression of Bclw in the testis appears to be restricted to elongating spermatids and Sertoli cells. Potential roles for Bclw in testicular function are discussed.
Ross
A J
AJ
Center for Molecular Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Waymire
K G
KG
Moss
J E
JE
Parlow
A F
AF
Skinner
M K
MK
Russell
L D
LD
MacGregor
G R
GR
D000367:Age Factors; D000595:Amino Acid Sequence; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D003001:Cloning, Molecular; D005640:Follicle Stimulating Hormone / Q000097:blood; D006720:Homozygote; D007150:Immunohistochemistry; D007248:Infertility, Male / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D011533:Proviruses / Q000235:genetics; D019105:Random Amplified Polymorphic DNA Technique; D017421:Sequence Analysis; D012708:Sertoli Cells / Q000378:metabolism; D013094:Spermatozoa / Q000254:growth & development* / Q000473:pathology; D013737:Testis / Q000473:pathology* / Q000502:physiology*; D014018:Tissue Distribution
D051017:Apoptosis Regulatory Proteins; C101155:Bcl2l2 protein, mouse; D011506:Proteins; D005640:Follicle Stimulating Hormone