Effects of an Igf1 gene null mutation on mouse reproduction.
Effects of an Igf1 gene null mutation on mouse reproduction.
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DOI：
10.1210/mend.10.7.8813730
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发表时间：
1996-07
影响因子：
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通讯作者：
J. Baker;M. Hardy;Jian Zhou;C. Bondy;F. Lupu;Anthony I . BelM;A. Efstratiadis
中科院分区：
文献类型：
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作者：
J. Baker;M. Hardy;Jian Zhou;C. Bondy;F. Lupu;Anthony I . BelM;A. Efstratiadis
编码胰岛素样生长因子1的Igf1基因的目标突变纯合子成年小鼠的两性都是不育的侏儒(大约是正常大小的30%)。由于侏儒症的程度，睾丸的体积比预期的要小，但精子生成仅维持在正常水平的18%。附睾总体上与减轻的体重几乎是异速生长的，但导管、输精管、精囊和前列腺的远端区域是残留的。尽管突变对附睾会产生影响，但获能精子能够在体外使野生型卵子受精。据推测，雄性突变体的不育是由于血清睾酮水平急剧下降(正常水平的18%)导致雄激素合成失败导致交配行为缺失所致。这种激素缺乏与突变的间质细胞的超微结构分析显示出显著的发育延迟有关，而器官培养中的分析表明，与野生型对照相比，睾丸实质基础和促黄体生成素刺激的睾酮产生减少。雌性突变体即使在注射促性腺激素后也无法排卵，这显然是她们不孕的主要原因，并拥有婴儿子宫，表现出戏剧性的发育不良，尤其是在子宫肌层。突变的表型表现与原位杂交检测到的胰岛素样生长因子I及其同源受体转录本在野生型生殖组织中的定位有关。
Both sexes of adult mice homozygous for a targeted mutation of the Igf1 gene, encoding insulin-like growth factor 1, are infertile dwarfs (approximately 30% of normal size). The testes are reduced in size less than expected from the degree of dwarfism but sustain spermatogenesis only at 18% of the normal level. The epididymides are overall nearly allometric to the reduced body weight, but the distal regions of the duct, vas deferens, seminal vesicles, and prostate are vestigial. Despite the mutational impact on the epididymis, capacitated sperm are able to fertilize wild type eggs in vitro. It is hypothesized that the infertility of male mutants is caused by failure of androgenization resulting in absence of mating behavior, due to drastically reduced levels of serum testosterone (18% of normal). This hormonal deficiency was correlated with an ultrastructural analysis of mutant Leydig cells revealing a significant developmental delay, while assays in organ culture showed that the basal and LH-stimulated production of testosterone by testicular parenchyma is reduced in comparison with wild type controls. The female mutants fail to ovulate even after administration of gonadotropins, which is apparently the primary cause of their infertility, and possess an infantile uterus that exhibits a dramatic hypoplasia especially in the myometrium. The phenotypic manifestations of the mutation were correlated with the localization of transcripts for insulin-like growth factor I and its cognate receptor in wild type reproductive tissues by in situ hybridization.