ANIMAL MODELS OF MALE INFERTILITY

特异性基因突变导致小鼠雄性不育 对精子发生或睾丸类固醇生成的影响。首要目标 建议的研究之一是阐明这些基因突变的作用。 性行为、精子功能和内分泌系统。这些研究 结合遗传学、行为科学、内分泌学和分子生物学 在对基因突变进行关键评估的生理学方法中 命名为半足多趾、高尾、甲状腺功能减退、矮小、侏儒和 粗短的。每只小鼠的生殖生物学参数如下 将被量化：交配行为，性唤醒，受精能力 体内和体外精子的活力、活力和速度， 用单抗检测精子成熟抗原的模式 血清促黄体生成素、卵泡刺激素、生长激素、催乳素、 甲状腺激素和睾丸素。拟议研究的一个方面是 荷尔蒙替代实验的设计可能提供对 特定生殖过程的荷尔蒙需求。这个 基因突变的后果将通过比较突变株来评估 老鼠和它们正常的兄弟姐妹。实验方法的威力在于 事实证明，不孕不育的主要区别是 小鼠和它的正常同胞是单基因突变。实验性的 结果将是重要的理解表型效应的 导致男性不育的基因突变。值得注意的是，这种基因 突变有可能成为重要的实验工具 破译成功男性所需的复杂过程网络 繁殖。突变小鼠也可能提供更好的动物模型。 特发性疾病的病因和治疗方法的研究 男性不育。 此外，还将利用雄性不育的突变小鼠模型 在为实现候选人的长期职业目标而设计的研究中： 白粉病遗传控制的分子基础研究进展 小鼠睾丸中的类固醇生成酶。讨论了一项计划，它将 提供必要的额外培训，使应聘者能够 在他的研究计划中加入类固醇生成的方法学 酶提纯和分子生物学。

Specific gene mutations induce male infertility in mice without observable effects on spermatogenesis or testicular steroidogenesis. The primary goal of the proposed studies is to elucidate the actions of these gene mutations on sexual behavior, sperm function, and the endocrine system. The studies combine genetics, behavioral science, endocrinology, and molecular biology in a physiological approach to the critical assessment of gene mutations named hemimelic extra toes, hightail, hypothyroid, little, pygmy, and stubby. The following parameters of the reproductive biology of each mouse will be quantified: mating behavior, sexual arousal, fertilizing capacity of sperm in vivo and in vitro, sperm viability, motility, and velocity, pattern of sperm maturation antigens as detected with monoclonal antibodies, and serum levels of LH, FSH, growth hormone, prolactin, thyroxine, and testosterone. One aspect of the proposed studies is the designing of hormone replacement experiments which may provide insight into hormonal requirements of specific reproductive processes. The ramifications of the gene mutations will be assessed by comparing mutant mice and their normal siblings. The power of the experimental approach is evidenced by the fact that the primary difference between the infertile mouse and its normal sibling is the single-gene mutation. The experimental results will be important for understanding the phenotypic effects of the gene mutations that cause male infertility. Significantly, the gene mutations have the potential of being important experimental tools for deciphering the complex network of processes required for successful male reproduction. The mutation mice may also provide superior animal models for investigations of the etiology and therapeutic treatments of idiopathic male infertility. In addition, the mutant mouse models of male infertility will be utilized in research designed to achieve a long-term career goal of the candidate: the elucidation of the molecular basis of the genetic control of steroidogenic enzymes in mouse testes. A progam is discussed that will provide the additional training necessary to permit the candidate to incorporate into his research program the methodologies of steroidogenic enzyme purification and molecular biology.