Mice homozygous for the s(1Acrg) deletion at the Ednrb lotus arrest at embr
yonic day 8.5. To determine the molecular basis of this defect, we initiate
d positional cloning of the s(1Acrg) minimal region. The mouse Uch-L3 (ubiq
uitin C-terminal hydrolase L3) gene was mapped within the s(1Acrg) minimal
region. Because Uch-L3 transcripts were present in embryonic structures rel
evant to the s(1Acrg) phenotype, we created a targeted mutation in Uch-L3 t
o address its role during development and its possible contribution to the
s(1Acrg) phenotype. Mice homozygous for the mutation UCh-L3(Delta 3-7) mere
viable, with no obvious developmental or histological abnormalities. Altho
ugh high levels of Uch-L3 RNA were detected in testes and thymus, Uch-L3(De
lta 3-7) homozygotes were fertile, and no defect in intrathymic T-cell diff
erentiation was detected. We conclude that the s(1Acrg) phenotype is either
complex and multigenic or due to the loss of another gene within the regio
n. We propose that Uch-L3 may be functionally redundant with its homologue
Uch-L1.