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人类和小鼠中的FAM241蛋白家族
Quinlan Doctrove1,2, Young Park2, Daniel G Calame3,4
1Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI, 48109, USA.
概括
在扩大溶酶体的镜中发现的FAM241B蛋白质,尽管其起源古老且表达广泛,但其功能尚不清楚. 在小鼠中,基因淘汰显示没有可见的表型,但观察到改变的基因表达.
科学领域:
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
- 进化生物学 进化生物学
背景情况:
- FAM241B蛋白属于FAM241家族,其特征是未知功能的保存域 (DUF4605).
- 这种蛋白质家族起源于鱼类之前,在脊椎动物中存在,在鸟类中特别缺少FAM241B.
研究的目的:
- 研究FAM241B蛋白及其家族成员的功能.
- 探索FAM241A和FAM241B的进化历史和表达模式.
主要方法:
- 全基因组无活化查
- 人类遗传学分析
- 在小鼠 (Fam241a,Fam241b,双击) 中进行基因淘汰研究.
- 鼠标大脑组织的RNA测序 (RNAseq)
- 对人类患者变体 (p.Val115Gly) 的分析.
主要成果:
- 在小鼠组织中,FAM241A和FAM241B被广泛表达.
- 对Fam241a和Fam241b的试验性淘汰,无论是单独还是组合,都没有在小鼠中产生可观察到的表型.
- 淘汰Fam241A和Fam241B并没有恶化FIG4无基因小鼠的表型.
- RNAseq揭示了双淘汰赛小鼠的大脑中特定基因的减少表达,包括Arke1e1和RnaseL.
- 人类FAM241B变种 (p.Val115Gly) 在发育迟缓的患者中被发现,尽管他们的纤维细胞表现出正常的溶酶体形态.
结论:
- 古代FAM241蛋白家族的精确分子功能仍未确定.
- 尽管在进化过程中保持和表达,但FAM241A和FAM241B似乎没有通过标准的淘汰表型在小鼠中检测到的基本作用.
- 需要进一步的研究来阐明FAM241蛋白质的生物学作用,可能涉及与细胞内膜网膜蛋白的相互作用或在特定发育环境中的作用.
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