Mus musculus with altered pre-mRNA processing

mRNA processing is an essential step of gene expression; its malfunction can lead to different degrees of physiological disorder, from subclinical disease to death. DIDO3, the larger protein encoded by the Dido1 gene, is required for accurate mRNA splicing and correct transcription termination. The deletion of Dido1 exon16, which encodes the carboxy-terminal half of DIDO3, results in early embryonic lethality in mouse. We have obtained mice bearing a Cre-LoxP conditional version of that deletion and studied the effects of ubiquitously inducing it in adult stages. DIDO3-deficient mice survive the deletion but suffer mild hepatitis, testicular degeneration and progressive ataxia, in association with systemic alterations in pre-mRNA processing. The present results offer insight into the distinct vulnerabilities that mouse organs present upon dampening of the pre-mRNA processing machinery.