Kobayashi Hiroaki, Takemoto Kenji, Sanbo Makoto, Hirabayashi Masumi, Hirabayashi Takahiro, Hirayama Teruyoshi, Kiyonari Hiroshi, Abe Takaya, Yagi Takeshi
KOKORO-Biology Group, Graduate School of Frontier Biosciences, Osaka University, Suita 565-0871, Japan.
Division of Biophysical Engineering, Department of Systems Science, School of Engineering Science, Osaka University, Toyonaka 565-8531, Japan.
iScience. 2022 Dec 8;26(1):105766. doi: 10.1016/j.isci.2022.105766. eCollection 2023 Jan 20.
Clustered protocadherin is a family of cell-surface recognition molecules implicated in neuronal connectivity that has a diverse isoform repertoire and homophilic binding specificity. Mice have 58 isoforms, encoded by , , and gene clusters, and mutant mice lacking all isoforms died after birth, displaying massive neuronal apoptosis and synapse loss. The current hypothesis is that the three specific γC-type isoforms, especially γC4, are essential for the phenotype, raising the question about the necessity of isoform diversity. We generated mutant mice that expressed the three γC-type isoforms but lacked all the other 55 isoforms. The mutants died immediately after birth, showing massive neuronal death, and or expression did not prevent apoptosis. Restoring the - and -clusters with the three alleles rescued the phenotype, suggesting that along with the three γC-type isoforms, other isoforms are also required for the survival of neurons and individual mice.
成簇原钙黏蛋白是一类参与神经元连接的细胞表面识别分子家族，具有多样的亚型库和嗜同性结合特异性。小鼠有58种亚型，由α、β和γ基因簇编码，缺乏所有亚型的突变小鼠出生后死亡，表现出大量神经元凋亡和突触丧失。目前的假说认为，三种特定的γC型亚型，尤其是γC4，对该表型至关重要，这就引发了关于亚型多样性必要性的问题。我们构建了表达三种γC型亚型但缺乏所有其他55种亚型的突变小鼠。这些突变小鼠出生后立即死亡，表现出大量神经元死亡，并且α或β表达并不能阻止细胞凋亡。用三个γ等位基因恢复α和β基因簇可挽救该表型，这表明除了三种γC型亚型外，其他亚型对于神经元和个体小鼠的存活也是必需的。
