Critical function of RA-GEF-2/Rapgef6, a guanine nucleotide exchange factor for Rap1, in mouse spermatogenesis.
Small GTPase Rap1 has been implicated in the proper differentiation of testicular germ cells. In the present study, we investigated the functional significance of RA-GEF-2/Rapgef6, a guanine nucleotide exchange factor for Rap1, in testicular differentiation using mice lacking RA-GEF-2. RA-GEF-2 was expressed predominantly on the luminal side of the seminiferous tubules in wild-type mice. No significant differences were observed in the body weights or hormonal parameters of RA-GEF-2(-)(/)(-) and wild-type mice. However, the testes of RA-GEF-2(-)(/)(-) male mice were significantly smaller than those of wild-type mice and were markedly atrophied as well as hypospermatogenic. The concentration and motility of epididymal sperm were also markedly reduced and frequently had an abnormal shape. The pregnancy rate and number of fetuses were markedly lower in wild-type females after they mated with RA-GEF-2(-)(/)(-) males than with wild-type males, which demonstrated the male infertility phenotype of RA-GEF-2(-)(/)(-) mice. Furthermore, a significant reduction and alteration were observed in the expression level and cell junctional localization of N-cadherin, respectively, in RA-GEF-2(-)(/)(-) testes, which may, at least in part, account for the defects in testicular differentiation and spermatogenesis in these mice.
Division of Urology, Department of Organs Therapeutics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Keisuke
K
Okada
Division of Urology, Department of Organs Therapeutics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Hideaki
H
Miyake
Division of Urology, Department of Organs Therapeutics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Kohei
K
Yamaguchi
Division of Urology, Department of Organs Therapeutics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Koji
K
Chiba
Division of Molecular Biology, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Kazuhiro
K
Maeta
Department of Biochemistry, Faculty of Pharmacy, Suez Canal University, El-shikh Zayed, Ismailia 41522, Egypt.
Shymaa E
SE
Bilasy
Division of Molecular Biology, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Hironori
H
Edamatsu
Division of Molecular Biology, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. Electronic address: kataoka@people.kobe-u.ac.jp.
Tohru
T
Kataoka
Division of Urology, Department of Organs Therapeutics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. Electronic address: masato@med.kobe-u.ac.jp.
Masato
M
Fujisawa
D000818:Animals; D001284:Atrophy; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D004822:Epididymis / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007150:Immunohistochemistry; D007248:Infertility, Male / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008855:Microscopy, Electron, Scanning; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013081:Sperm Motility / Q000235:genetics / Q000502:physiology; D013091:Spermatogenesis / Q000235:genetics / Q000502:physiology*; D013094:Spermatozoa / Q000378:metabolism / Q000648:ultrastructure; D013737:Testis / Q000378:metabolism / Q000473:pathology; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism*
D015820:Cadherins; D020662:Guanine Nucleotide Exchange Factors; C588099:Rapgef6 protein, mouse; D020827:rap1 GTP-Binding Proteins
Male infertility; RA-GEF-2; Rap1; Small GTPases; Spermatogenesis