The tail suspension test (TST) and forced swimming test (FST) are widely used for assessing antidepressant activity and depression-like behavior. We found that CS mice show negligible immobility in inescapable situations. Quantitative trait locus (QTL) mapping using CS and C57BL/6J mice revealed significant QTLs on chromosomes 4 (FST) and 5 (TST and FST). To identify the quantitative trait gene on chromosome 5, we narrowed the QTL interval to 0.5 Mb using several congenic and subcongenic strains. Ubiquitin-specific peptidase 46 (Usp46) with a lysine codon deletion was located in this region. This deletion affected nest building, muscimol-induced righting reflex and anti-immobility effects of imipramine. The muscimol-induced current in the hippocampal CA1 pyramidal neurons and hippocampal expression of the 67-kDa isoform of glutamic acid decarboxylase were significantly decreased in the Usp46 mutant mice compared to control mice. These phenotypes were rescued in transgenic mice with bacterial artificial chromosomes containing wild-type Usp46. Thus, Usp46 affects the immobility in the TST and FST, and it is implicated in the regulation of GABA action.
A gene-encoding ligand for deletion of T cells bearing TcRV beta 6 and V beta 8.1 cosegregates a new mammary tumor provirus locus, Mtv-50 in NC mice. The sequence of the open reading frame (ORF) in the 3' long terminal repeat (LTR) of Mtv-50 was strikingly similar to those of Mtv-7, Mtv-43 and exogenous mouse mammary tumor virus (SW) with properties of minor lymphocyte stimulating antigen 1a. Consistent with previous reports, clonal deletion of mature thymocytes bearing TcRV beta 6 was defective during the early postnatal period of mice carrying Mtv-50. Appreciable levels of mRNA corresponding to common Mtv ORF and Mtv-6 ORF were expressed in the neonatal thymus, while little, if any, mRNA corresponding to Mtv-50 ORF was detected in the thymus at the early postnatal stage. Delay in expression of Mtv-50 ORF during the postnatal period may be responsible for the failure of clonal deletion of V beta 6-T cells in the early postnatal life of mice carrying Mtv-50.
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