The novel dominant mutation Dspd leads to a severe spermiogenesis defect in mice.
Spermiogenesis is a complex process that is regulated by a plethora of genes and interactions between germ and somatic cells. Here we report a novel mutant mouse strain that carries a transgene insertional/translocational mutation and exhibits dominant male sterility. We named the mutation dominant spermiogenesis defect (Dspd). In the testes of Dspd mutant mice, spermatids detached from the seminiferous epithelium at different steps of the differentiation process before the completion of spermiogenesis. Microinsemination using spermatids collected from the mutant testes resulted in the birth of normal offspring. These observations indicate that the major cause of Dspd infertility is (are) a defect(s) in the Sertoli cell-spermatid interaction or communication in the seminiferous tubules. Fluorescent in situ hybridization (FISH) analysis revealed a translocation between chromosomes 7F and 14C at the transgene insertion site. The deletion of a genomic region of chromosome 7F greater than 1 megabase and containing at least six genes (Cttn, Fadd, Fgf3, Fgf4, Fgf15, and Ccnd1) was associated with the translocation. Cttn encodes the actin-binding protein cortactin. Immunohistochemical analysis revealed localization of cortactin beside elongated spermatids in wild-type testes; abnormality of cortactin localization was found in mutant testes. These data suggest an important role of cortactin in Sertoli cell-spermatid interactions and in the Dspd phenotype.
Kai
Masayuki
M
Division for Gene Research, Center for Biological Resources and Informatics, Tokyo Institute of Technology, Midori-ku, Yokohama 226-8501, Japan.
Irie
Masahito
M
Okutsu
Tomohisa
T
Inoue
Kimiko
K
Ogonuki
Narumi
N
Miki
Hiromi
H
Yokoyama
Minesuke
M
Migishima
Rika
R
Muguruma
Kaori
K
Fujimura
Hisako
H
Kohda
Takashi
T
Ogura
Atsuo
A
Kaneko-Ishino
Tomoko
T
Ishino
Fumitoshi
F
D000818:Animals; D002450:Cell Communication / Q000235:genetics; D002454:Cell Differentiation; D051356:Cortactin; D004251:DNA Transposable Elements; D005799:Genes, Dominant; D007248:Infertility, Male / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D007315:Insemination, Artificial; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D012708:Sertoli Cells; D013087:Spermatids / Q000473:pathology; D013091:Spermatogenesis / Q000235:genetics*; D013737:Testis / Q000378:metabolism; D019076:Transgenes / Q000235:genetics; D014178:Translocation, Genetic
D051356:Cortactin; C495869:Cttn protein, mouse; D004251:DNA Transposable Elements; D008840:Microfilament Proteins