Spontaneous Mutation in2310061I04RikResults in Reduced Expression of Mitochondrial Genes and Impaired Brain Myelination

Abstract

SummaryHere, we describe a spontaneous mouse mutant with a deletion in a predicted gene2310061I04Rik(Rik) of unknown function located on chromosome 17. A 59 base pair long deletion occurred in the first intron of theRikgene and disrupted its expression.Riknullmice were born healthy and appeared anatomically normal up to two weeks of age. After that, these mice showed inhibited growth, ataxic gait, and died shortly after postnatal day 24 (P24). Transcriptome analysis at P14 and P23 revealed significantly reduced expression of mitochondrial genes inRiknullbrains compared to wild type controls includingmt-Nd4,mt-Cytb,mt-Nd2,mt-Co1,mt-Atp6,and others. Similarly, genes specific for myelinating oligodendrocytes also showed reduced expression in P23Riknullbrains compared to controls. Histological examination of anterior thalamic nuclei demonstrated decreased myelination of anteroventral nuclei but not of anterodorsal nuclei in P23Riknullmice. Myelination of the anterior commissure was also impaired and displayed extensive vacuolation. Consistent with these findings, immunohistochemistry showed reduced expression of Opalin, a glycoprotein expressed in differentiated oligodendrocytes. Taken together, these results suggest that RIK is important for oligodendrocyte maturation, and myelination in the developing brain.