Expression and Functional Analysis of Uch-L3 during Mouse Development

Howard Hughes Medical Institute and Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
Molecular and Cellular Biology (Impact Factor: 4.78). 05/2000; 20(7):2498-504. DOI: 10.1128/MCB.20.7.2498-2504.2000
Source: PubMed


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
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.

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Available from: Ekaterina Semenova
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    • "A unique feature of UCH-L3 is that this enzyme has dual hydrolase specificity towards Ub and Nedd8 [8]. UCH-L3 is expressed ubiquitously in all tissues but the expression of UCH-L1 is restricted to the testes, ovaries, and neurons [4] [6] [9]. "
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    • "Meiotic pachytene spermatocytes and postmeiotic spermatids; cauda epididymis Sperm quality control during epididymal maturation Mus musculus [48] [109] [110] Uch-L4 All tissues, with testis included Mus musculus [111] Uch-L5 Spermatocytes and spermatids Mus musculus [112] CYLD Control of spermatogenetic cell apoptosis and spermatogenesis progression via RIP1/NF-kappaB signalling axis Mus musculus [113] * Indicates " also known as DnaJB13 " . "
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    • "To date, the only isopeptidase known to function exclusively in NEDD8 processing and deconjugation is the C48 family peptidase DEN1/NEDP1/SENP8 from Drosophila, and human (Figure 3; Gan-Erdene et al., 2003; Mendoza et al., 2003; Wu et al., 2003; Shen et al., 2005; Chan et al., 2008; Shin et al., 2011). However, mouse knockouts of UCHL3 or Drosophila and Aspergillus knockouts of DEN1 are viable although NEDD8 and neddylation are essential in the respective organisms (Kurihara et al., 2000; Chan et al., 2008; Christmann et al., 2013). These findings suggest that mutants of these processing enzymes cannot be fully impaired in NEDD8 processing. "
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