Setd1a哈普洛缺陷对发育和成人行为的性别依赖性影响
Matthew L Bosworth1, Anthony R Isles1, Lawrence S Wilkinson1,2,3
1Division of Psychological Medicine and Clinical Neuroscience, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, United Kingdom.
PloS one
|August 14, 2024
概括
在SETD1A中功能突变的丧失与神经发育障碍有关. 这项针对Setd1a哈普洛因不足小鼠的研究揭示了性别特异的发育和行为变化,支持其作为精神分裂症模型的使用.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 遗传学 是一个
- 发展生物学 发展生物学
背景情况:
- 基因组甲基转移酶SETD1A中的功能丧失 (LoF) 突变与神经发育障碍有关,包括精神分裂症.
- 了解SETD1A在大脑发育和功能中的确切作用对于阐明这些疾病的生物学基础至关重要.
研究的目的:
- 在小鼠模型中研究Setd1a哈普洛缺陷的发育和行为后果.
- 探索与Setd1a缺乏相关的表型中的潜在与性别相关的差异.
- 评估Setd1a的实用性,作为精神分裂症的模型.
主要方法:
- 产生和分析Setd1a的哈普洛因不足小鼠 (Setd1a+/-).
- 评估产前和产后发育指数,包括胎盘和体重.
- 成年人的行为测试,包括声学惊反应,脉冲前抑制,焦虑测试 (开放场,升高加迷宫) 和记忆测试.
- 胚胎全脑RNA测序以识别基因表达变化.
主要成果:
- 在Setd1a+/-小鼠中观察到胎盘和体重发展的性别特异性差异.
- RNA-seq揭示了胚胎大脑中线粒体相关的基因表达变化的丰富.
- 成年雄性Setd1a+/-小鼠表现出增强的声学惊反应,对RISPERIDONE不敏感,但对HALOPERIDOL不敏感.
- 减少前脉冲抑制,精神分裂症相关的表型,在两性中都观察到,并没有被抗精神病药物所拯救.
- 设定1a的哈普隆缺陷导致两性中焦虑类行为增加,而不会影响运动技能或记忆力.
结论:
- 在小鼠中Settd1a的哈普洛缺陷重新总结了与精神分裂症相关的几个表型,支持其作为疾病模型的使用.
- 这项研究强调了Setd1a缺乏的性别特异性发育轨迹和行为结果.
- 研究结果表明,线粒体功能障碍和改变焦虑回路在Setd1a相关疾病的神经生物学中的潜在作用.
相关概念视频
01:33Pleiotropy
40.3K
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
40.3K
01:43Sex-linked Disorders
101.8K
Like autosomes, sex chromosomes contain a variety of genes necessary for normal body function. When a mutation in one of these genes results in biological deficits, the disorder is considered sex-linked.
101.8K
02:50Dosage Compensation
6.1K
In animals, gender is determined by the number and type of sex chromosome. For example, human females have two X chromosomes, and males have one X and one Y chromosome, whereas C.elegans with one X chromosome is a male, and the one with two X chromosomes is a hermaphrodite.
In addition to sexual development, the X chromosome has genes involved in autosomal functions such as brain development and the immune system. Therefore, males and females with distinct numbers of X chromosomes will...
In addition to sexual development, the X chromosome has genes involved in autosomal functions such as brain development and the immune system. Therefore, males and females with distinct numbers of X chromosomes will...
6.1K
01:28Human Genetics
551
Human genetics provides a profound framework for understanding the interplay between genetic predispositions and human psychology. At the heart of this discipline lies the study of how genes influence physical traits, behaviors, and susceptibility to diseases. Each person carries a unique genetic code that subtly or significantly shapes their psychological and behavioral landscape.
The complex relationship between genetics and psychology is observable through common biological components such...
The complex relationship between genetics and psychology is observable through common biological components such...
551
01:35Pedigree Analysis
84.1K
Overview
84.1K
02:30Genomic Imprinting and Inheritance
34.2K
Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
34.2K