Deletion of the Parkin co-regulated gene causes defects in ependymal ciliary motility and hydrocephalus in the quakingviable mutant mouse

摘要: The quakingviable mouse (qkv) is a spontaneous recessive mutant with deletion of approximately 1.1 Mb in the proximal region chromosome 17. affects expression three genes; quaking (Qk), Parkin-coregulated gene (Pacrg) and parkin (Park2). resulting phenotype, which includes dysmyelination central nervous system male sterility, due to reduced Qk complete lack Pacrg expression, respectively. required for correct development spermatozoan flagella, specialized type motile cilia. In vertebrates, cilia are multiple functions related cellular movement or media over stationary cell surface. To investigate potential role PACRG we analysed qkv mice evidence cilial dysfunction. Histological magnetic resonance imaging analyses demonstrated that were affected by acquired, communicating hydrocephalus (HC). Structural analysis ependymal 9 + 2 arrangement axonemal microtubules was intact both density ciliated cells length similar wild-type littermates. Cilia function studies showed reduction beat frequency mediated flow compared littermate controls. Moreover, transgenic necessary sufficient this deficit rescue HC phenotype mutant. This study provides novel vivo may be involved pathogenesis human ciliopathies, such as HC, asthenospermia primary ciliary dyskinesia.