PHENOTYPIC EXPRESSION OF AN OXYTOCIN PEPTIDE NULL MUTATION IN MICE

小鼠中催产素肽无效突变的表型表达

• 批准号: 6277511
• 负责人: JAMES Timothy WINSLOW
• 金额: $ 3.54万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6277511
• 关键词: Mammalia; Primates; cognition; nervous system; psychology

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.

同源重组技术用于产生小鼠， 催产素基因缺失 放射免疫组织化学 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 在催产素缺失的杂合子小鼠中表达。 催产素 敲除小鼠交配、分娩并表现出正常母性行为， 然而，乳汁排出被中断。 AVP基因表达无明显变化。 在OT敲除小鼠中增加，OT受体也没有变化。 用OT拮抗剂给予ICV的慢性治疗也没有改变 基因敲除小鼠的母性行为。 缺乏对性和 母性行为可能与品系和物种差异有关， 潜在的神经机制 该项目的目标是 产生OT敲除的综合行为表型 老鼠. 检查社会和认知行为的其他方面 在这些动物身上进行。 初步结果包括： 幼犬超声波叫声率下降，攻击性增加 在纯合子敲除小鼠中。 这些分析包括比较 具有C57 BL/6 J和 129/J背景菌株，以控制潜在的 背景污染 其他研究考察了 父母基因型对后代行为发育的影响 无效突变 初步研究结果表明，父母的因素可能 "拯救"一些行为缺陷。 这些研究表明， 遗传背景、父母影响和 发展补偿在最终的行为表达， 突变表型