PHENOTYPIC EXPRESSION OF AN OXYTOCIN PEPTIDE NULL MUTATION IN MICE

同源重组技术被用来产生小鼠 催产素基因缺失。放射免疫分析免疫组织化学 染色和原位杂交证实催产素不是 在这些小鼠中表达，催产素的中间水平是 在杂合的小鼠中表达为催产素缺失。催产素 基因敲除的小鼠交配、生育并表现出正常的母性行为， 然而，乳汁排出会受到干扰。AVP基因表达未见明显变化 在OT基因敲除的小鼠中，OT受体也没有变化。 脑室注射催产素拮抗剂的慢性治疗也不会改变 基因敲除小鼠的母性行为。缺乏对性和性行为的影响 母性行为可能与品系和物种差异有关 潜在的神经机制。这个项目的目标是 生成OT基因敲除的综合行为表型 老鼠。考察社会和认知行为的其他方面 正在这些动物体内进行。P最新发现包括 幼犬超声波呼叫率降低，攻击性增加 在纯合子基因敲除小鼠中。这些分析包括比较 嵌合基因敲除和野生型小鼠与C57BL/6J和 129/J背景株控制潜势的努力 背景污染。更多的研究考察了 亲本基因对子代行为发育的影响 零突变。初步研究结果表明，父母因素可能 “拯救”一些行为缺陷。这些研究表明， 遗传背景、亲本影响和遗传因素的复杂交互作用 终极行为表达中的发育补偿 突变表型。

Homologous recombination techniques were used to produce mice with an oxytocin gene deletion. Radiommunoassay immunohistochemical staining, and in situ hybridization confirmed that oxytocin is not expressed in these mice and that intermediate levels of oxytocin are expressed in mice heterozygous for the oxytocin deletion. Oxytocin knock-out mice mate, give birth, and express normal maternal behavior, however milk ejection is disrupted. AVP gene expression was not increased in OT knockout mice, nor were there changes in OT receptors. Chronic treatment with an OT antagonist given ICV also did not alter maternal behavior in knockout mice. The lack of effects on sexual and maternal behaviors may be related to strain and species differences in underlying neural mechanisms. The objective of this project is to generate a comprehensive behavioral phenotype of the OT knockout mouse. Examination of other aspects of social and cognitive behavior are on-going in these animals. P reliminary findings include a decreased rate of pup ultrasonic calls and an increase in aggression in the homozygous knockout mice. These analyses include comparisons of the chimeric knockout and wild-type mice with the C57BL/6J and 129/J background strains in an effort to control for potential background contamination. Additional studies examine the influence of parental genotype on the behavioral development of offspring with the null mutation. Initial findings suggest that parental factors may "rescue" some behavioral deficits. These studies demonstrate the complex interaction of genetic background, parental influence and developmental compensation in the ultimate behavioral expression of a mutational phenotype.