Expression and Functional Analysis ofUch-L3 during Mouse Development

ABSTRACT Mice homozygous for the s1Acrg deletion at the Ednrb locus arrest at embryonic day 8.5. To determine the molecular basis of this defect, we initiated positional cloning of the s1Acrg minimal region. The mouseUch-L3 (ubiquitin C-terminal hydrolase L3) gene was mapped within the s1Acrg minimal region. BecauseUch-L3 transcripts were present in embryonic structures relevant to the s1Acrg phenotype, we created a targeted mutation in Uch-L3 to address its role during development and its possible contribution to thes1Acrg phenotype. Mice homozygous for the mutation Uch-L3Δ3-7 were viable, with no obvious developmental or histological abnormalities. Although high levels of Uch-L3 RNA were detected in testes and thymus,Uch-L3Δ3-7 homozygotes were fertile, and no defect in intrathymic T-cell differentiation was detected. We conclude that the s1Acrg phenotype is either complex and multigenic or due to the loss of another gene within the region. We propose that Uch-L3 may be functionally redundant with its homologue Uch-L1.