The gene encoding bone morphogenetic protein 8B is required for the initiation and maintenance of spermatogenesis in the mouse

被引:211
作者
Zhao, GQ
Deng, K
Labosky, PA
Liaw, L
Hogan, BLM
机构
[1] VANDERBILT UNIV, SCH MED, HOWARD HUGHES MED INST, NASHVILLE, TN 37232 USA
[2] VANDERBILT UNIV, SCH MED, DEPT CELL BIOL, NASHVILLE, TN 37232 USA
关键词
BMP8b; targeted gene inactivation; male germ cell; spermatogenesis; testis degeneration; fertility;
D O I
10.1101/gad.10.13.1657
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Bone morphogenetic protein 8B (BMPBB) is a member of the TGF beta superfamily of growth factors. In the mouse, Bmp8b is expressed in male germ cells of the testis and trophoblast cells of the placenta, suggesting that it has a role in spermatogenesis and reproduction. To investigate these possibilities, we have generated mice with a targeted mutation in Bmp8b. Here, we show that homozygous Bmp8b(tm1blh) mutant males exhibit variable degrees of germ-cell deficiency and infertility. Detailed analysis reveals two separable defects in the homozygous mutant testes. First, during early puberty (2 weeks old or younger) the germ cells of all homozygous mutants either fail to proliferate or show a marked reduction in proliferation and a delayed differentiation. Second, in adults, there is a significant increase in programmed cell death (apoptosis) of spermatocytes, leading to germ-cell depletion and sterility. Sertoli cells and Leydig cells appear relatively unaffected in mutants. This study therefore provides the first genetic evidence that a murine germ cell-produced factor, BMP8B, is required for the resumption of male germ-cell proliferation in early puberty, and for germ-cell survival and fertility in the adult.
引用
收藏
页码:1657 / 1669
页数:13
相关论文
共 60 条
[1]  
[Anonymous], 1994, MANIPULATING MOUSE E
[2]  
BARDIN CW, 1993, CELL MOL BIOL TESTIS, P189
[3]   MAPPING OF GENES FOR INHIBIN SUBUNIT-ALPHA, SUBUNIT-BETA-A, AND SUBUNIT-BETA-B ON HUMAN AND MOUSE CHROMOSOMES AND STUDIES OF JS']JSD MICE [J].
BARTON, DE ;
YANGFENG, TL ;
MASON, AJ ;
SEEBURG, PH ;
FRANCKE, U .
GENOMICS, 1989, 5 (01) :91-99
[4]   JUVENILE SPERMATOGONIAL DEPLETION (JS']JSD) - A GENETIC-DEFECT OF GERM-CELL PROLIFERATION OF MALE-MICE [J].
BEAMER, WG ;
CUNLIFFEBEAMER, TL ;
SHULTZ, KL ;
LANGLEY, SH ;
RODERICK, TH .
BIOLOGY OF REPRODUCTION, 1988, 38 (04) :899-908
[5]   MULLERIAN-INHIBITING SUBSTANCE FUNCTION DURING MAMMALIAN SEXUAL DEVELOPMENT [J].
BEHRINGER, RR ;
FINEGOLD, MJ ;
CATE, RL .
CELL, 1994, 79 (03) :415-425
[6]   Sertoli cell signaling by Desert hedgehog regulates the male germline [J].
Bitgood, MJ ;
Shen, LY ;
McMahon, AP .
CURRENT BIOLOGY, 1996, 6 (03) :298-304
[7]   HEDGEHOG AND BMP GENES ARE COEXPRESSED AT MANY DIVERSE SITES OF CELL-CELL INTERACTION IN THE MOUSE EMBRYO [J].
BITGOOD, MJ ;
MCMAHON, AP .
DEVELOPMENTAL BIOLOGY, 1995, 172 (01) :126-138
[8]   IDENTIFICATION OF A STIMULATOR OF STEROID-HORMONE SYNTHESIS ISOLATED FROM TESTIS [J].
BOUJRAD, N ;
OGWUEGBU, SO ;
GARNIER, M ;
LEE, CH ;
MARTIN, BM ;
PAPADOPOULOS, V .
SCIENCE, 1995, 268 (5217) :1609-1612
[9]   EVIDENCE FOR GERM-CELL CONTROL OF SERTOLI-CELL FUNCTION IN 3 MODELS OF GERM-CELL DEPLETION IN ADULT-RAT [J].
BOUJRAD, N ;
HOUCHEREAUDEREVIERS, MT ;
CARREAU, S .
BIOLOGY OF REPRODUCTION, 1995, 53 (06) :1345-1352
[10]   SOMATOMEDIN-C/INSULIN-LIKE GROWTH-FACTOR 1-LIKE MATERIAL SECRETED BY PORCINE SERTOLI CELLS-INVITRO - CHARACTERIZATION AND REGULATION [J].
CHATELAIN, PG ;
NAVILLE, D ;
SAEZ, JM .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1987, 146 (03) :1009-1017