缺少IQCH会导致人类和小鼠的男性不孕
Tiechao Ruan1,2, Ruixi Zhou1,2, Yihong Yang3
1Key Laboratory of Obstetrics, Gynecologic and Pediatric Diseases and Birth Defects of the Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China.
eLife
|July 19, 2024
概括
一个新型的基因,智商模式含有H (IQCH),对男性生育能力至关重要. 在IQCH的突变通过影响精子结构和功能导致不孕,突出其在精子生成中的作用.
科学领域:
- 生殖生物学 生殖生物学
- 分子遗传学 分子遗传学
- 细胞生物学 细胞生物学
背景情况:
- 含有智商模式的蛋白质与calmodulin (CaM) 相互作用,对生物过程至关重要.
- 含有智商模式的蛋白质在精子生成中的特定作用仍然在很大程度上未被描述.
研究的目的:
- 研究新型智商基因含H (IQCH) 在男性生育能力和精子生成中的功能.
- 阐明IQCH在精子发育中的作用背后的分子机制.
主要方法:
- 在男性不孕症的人类家庭中识别IQCH中的功能丧失突变.
- 使用CRISPR-Cas9技术进行功能验证,生成Iqch淘汰赛 (KO) 鼠标.
- 对KO小鼠的精子结构 (轴体,线粒体,体) 和生育能力的分析.
主要成果:
- 一个患有男性不孕症的中国家庭呈现出裂纹的鞭毛轴突和与IQCH突变相关的异常线粒体结构.
- IQCH KO雄性小鼠表现出显著受损的生育能力,反映出人类表型,表现出缺陷的体活性和轴突和线粒体的结构异常.
- 发现IQCH结合了CaM并调节了RNA结合蛋白的表达,特别是HNRPAB,这对精子生成至关重要.
结论:
- IQCH 是男性生育能力的关键基因,突变导致明显的精子缺陷.
- 这项研究将智商模式含有蛋白质的已知功能扩展到生殖过程中.
- 这些发现为遗传咨询和诊断男性不孕症提供了宝贵的见解.
相关概念视频
Infertility in Males
258
Male infertility affects millions of couples worldwide, arising from various factors that impact different stages of the reproductive process. An endocrine imbalance resulting from conditions like hypogonadism, Klinefelter syndrome, or pituitary disorders can disrupt hormone levels and reduce sperm production. Testicular defects, such as tumors, cryptorchidism, atrophic testes, abnormal sperm morphology, and low sperm count or motility, may arise due to genetic factors, structural...
258
The Y Chromosome Determines Maleness
6.5K
The Y chromosome is a sex chromosome found in several vertebrates and mammals, including humans. In addition to 22 pairs of autosomes, the human males have one X chromosome and one Y chromosome. In these organisms, the presence or absence of the Y chromosome determines the development of male traits.
Evolution
Around 300 million years ago, the two sex chromosomes diverged from two identical autosomal chromosomes. Over time, the Y chromosome has lost most of its genes, shrinking in size....
Evolution
Around 300 million years ago, the two sex chromosomes diverged from two identical autosomal chromosomes. Over time, the Y chromosome has lost most of its genes, shrinking in size....
6.5K
Sex-linked Disorders
101.9K
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.
101.9K
Dosage 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
X-Inactivation
38.3K
The human X chromosome contains over ten times the number of genes as in the Y chromosome. Since males have only one X chromosome, and females have two, one might expect females to produce twice as many of the proteins, with undesirable results.
38.3K
X and Y Chromosomes
25.6K
Among mammals, the gender of an organism is determined by the sex chromosomes. Humans have two sex chromosomes, X and Y. Every human diploid cell has 22 pairs of autosomes and one pair of sex chromosomes. A human female has two X chromosomes, while a male has one X chromosome and one Y chromosome.
The germline cells such as egg and sperm cells carry only half the number of chromosomes, i.e., 22 autosomes and one sex chromosome. All eggs have an X chromosome, while sperm cells can carry an X or...
The germline cells such as egg and sperm cells carry only half the number of chromosomes, i.e., 22 autosomes and one sex chromosome. All eggs have an X chromosome, while sperm cells can carry an X or...
25.6K


