Fraternal Birth Order Effects on Behavior

兄弟出生顺序对行为的影响

基本信息

批准号：
7643161
负责人：
S MARC BREEDLOVE
金额：
$ 17.1万
依托单位：
MICHIGAN STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-07-01 至 2012-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7643161
关键词：
Accounting Affect Androgens Animal Model Animals Antibodies Antigens Attention Deficit Disorder Auditory Autistic Disorder Behavior Behavioral Birth Birth Order Brothers Caring Data Data Set Development Disease Dyslexia Embryo Epigenetic Process Exposure to Female Fostering Future Generations Genes Human Immune system Implant Incidence Lead Learning Life Light Mammals Maternal Behavior Mediating Modeling Monitor Morphology Mothers Mus Nervous system structure Neurodevelopmental Disorder Partner in relationship Pilot Projects Principal Investigator Process Risk Factors Sex Characteristics Siblings Sister Social Behavior Social Interaction Son Structure Surface Testing Testosterone Toxin Uncertainty Weaning Work autism spectrum disorder boys experience girls high risk human male in utero innovation insight male mouse model neurodevelopment novel offspring public health relevance pup relating to nervous system research study response sex social

项目摘要

DESCRIPTION (provided by applicant): We have developed a new mouse model that demonstrates that the sex of a litter carried by a mouse dam can affect social behavior and sensorimotor processing in her subsequent offspring. Mouse dams are implanted with a litter of all male embryos or a litter of all female embryos and allowed to carry this first litter to term and wean the offspring. The dams are then mated to produce a second litter consisting of both sexes. We find that males in the second generation display differences in behavior depending on whether all their older siblings were brothers or sisters. Many of these behavioral differences are reminiscent of autism spectrum disorder in humans. Compared to male mice with older sisters, male mice with older brothers display an exaggerated startle response, inappropriate social interactions, avoidance of novel objects, and difficulty in auditory processing. Each of these behaviors represent an important component of autism spectrum disorder in humans. Thus we may have stumbled upon a previously unsuspected risk factor for autism in males: the number of older brothers. In addition, the effect of older brothers on the development of subsequent brothers may represent a contributing factor to the greater incidence of other neurodevelopmental disorders, such as ADD and dyslexia, in boys than in girls. We would like to explore our mouse model for this "fraternal birth order" (FBO) effect. Understanding how older brothers affect behaviors in our mice may shed light on how other factors (including genes and toxin) might lead to neurodevelopmental disorders in humans. We will investigate possible mechanisms that might underlie these phenomena, including the possibility that the maternal immune system may be directing antibodies to male-specific antigens in subsequent sons, and that maternal experience caring for pups of one sex may affect subsequent maternal care of subsequent sons. PUBLIC HEALTH RELEVANCE We will investigate a mouse model for the effects of older brothers on behaviors that typify autistic spectrum disorder. Preliminary evidence suggests that a mammalian mother that has carried a son to term may produce antibodies that attack the nervous system of subsequent sons in utero. By learning how older brothers increase autistic-like behaviors in mice, we may gain insight into the development of autism and possible therapies for this disorder.

描述（由申请人提供）：我们开发了一种新的鼠标模型，该模型表明，小鼠大坝携带的垃圾的性别会影响她随后的后代中的社会行为和感觉运动处理。将小鼠大坝植入所有雄性胚胎或所有雌性胚胎的垃圾的垃圾中，并允许将第一个垃圾带到后代和断奶后代。然后，将大坝交配以产生由两个性别组成的第二个垃圾。我们发现第二代男性在行为上表现出差异，具体取决于所有年长的兄弟姐妹是兄弟姐妹。这些行为差异中有许多让人联想到人类的自闭症谱系障碍。与有年长姐妹的雄性小鼠相比，患有哥哥的雄性小鼠表现出夸张的惊吓反应，不适当的社交互动，避免对新物体的物体以及听觉处理的困难。这些行为中的每一个都代表了人类自闭症谱系障碍的重要组成部分。因此，我们可能已经偶然发现了以前未受关注的男性自闭症风险因素：哥哥的数量。此外，哥哥对随后的兄弟的发展的影响可能代表了男孩中其他神经发育障碍（例如ADD和阅读障碍）更大的因素。我们想以这种“兄弟出生顺序”（FBO）效应探索我们的鼠标模型。了解哥哥如何影响我们的小鼠行为可能会揭示其他因素（包括基因和毒素）如何导致人类神经发育障碍。我们将研究可能是这些现象的基础的可能机制，包括母体免疫系统可能在随后的儿子中指导对男性特异性抗原的抗体，并且照顾一个性别的幼犬的母性经验可能会影响后续儿子的后续母亲护理。公共卫生相关性，我们将研究鼠标模型，以实现哥哥对典型自闭症谱系障碍的行为的影响。初步证据表明，将儿子带到术语的哺乳动物母亲可能会产生抗体，以攻击子宫内随后的儿子的神经系统。通过了解哥哥如何增加小鼠的自闭症行为，我们可能会深入了解自闭症的发展和这种疾病的可能疗法。