The <i>Clp1</i> R140H mutation alters tRNA metabolism and mRNA 3′ processing in mouse models of pontocerebellar hypoplasia

Abstract

Significance Mutation of CLP1 causes pontocerebellar hypoplasia type 10 (PCH10), a neurodegenerative disorder associated with intellectual and motor disability. We made two mouse models of PCH10: one homozygous for the mutation found in patients and one heterozygous for this mutation and a null allele. Mutant mice had motor impairments and neurodegeneration in the spinal cord and cerebellum. Mutants also had altered tRNA metabolism; however, it is not clear whether these alterations contribute to pathogenesis. In addition, mutation of Clp1 resulted in altered poly(A) site selection and gene expression, suggesting that the role of CLP1 in mRNA 3′ end processing could be a promising avenue for future research into the pathogenesis of PCH10.