title: Expression and functional analysis of Uch-L3 during mouse development.
abstract: Mice homozygous for the s(1Acrg) 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 s(1Acrg) minimal region. The mouse Uch-L3 (ubiquitin C-terminal hydrolase L3) gene was mapped within the s(1Acrg) minimal region. Because Uch-L3 transcripts were present in embryonic structures relevant to the s(1Acrg) phenotype, we created a targeted mutation in Uch-L3 to address its role during development and its possible contribution to the s(1Acrg) phenotype. Mice homozygous for the mutation Uch-L3(Delta3-7) were viable, with no obvious developmental or histological abnormalities. Although high levels of Uch-L3 RNA were detected in testes and thymus, Uch-L3(Delta3-7) homozygotes were fertile, and no defect in intrathymic T-cell differentiation was detected. We conclude that the s(1Acrg) 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.
authors.affiliation: Howard Hughes Medical Institute and Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Kurihara
authors.forename: E
authors.initials: E
authors.lastname: Semenova
authors.forename: J M
authors.initials: JM
authors.lastname: Levorse
authors.forename: S M
authors.initials: SM
authors.lastname: Tilghman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D003001:Cloning, Molecular; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D005865:Gestational Age; D006720:Homozygote; D017403:In Situ Hybridization; D008285:Major Histocompatibility Complex / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D016415:Sequence Alignment; D013601:T-Lymphocytes / Q000378:metabolism; D013869:Thiolester Hydrolases / Q000235:genetics* / Q000378:metabolism; D043222:Ubiquitin Thiolesterase
chemical_list: D012333:RNA, Messenger; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase