| First Author | Jun K | Year | 2000 |
| Journal | Mamm Genome | Volume | 11 |
| Issue | 10 | Pages | 843-8 |
| PubMed ID | 11003697 | Mgi Jnum | J:64725 |
| Mgi Id | MGI:1889915 | Doi | 10.1007/s003350010176 |
| Citation | Jun K, et al. (2000) Insertion of a retroviral solo long terminal repeat in mdr-3 locus disrupts mRNA splicing in mice. Mamm Genome 11(10):843-8 |
| abstractText | Previously, the abermectin-induced neurotoxicity of subpopulation of CF-1 mice was shown to be caused by the deficiency of mdr-3 P-glycoprotein. Here, we have characterized the molecular nature of the mdr-3 gene mutation in this subpopulation of CF-1 mice. The size of mdr-3 mRNA transcript from ivermectin-sensitive mutant mice was different from that of wild-type mice. Sequence analysis of RT-PCR products isolated from the mutant brain disclosed that the exon 23 of the mdr-3 gene is deleted or altered in the transcripts. The analysis of the genomic locus revealed an insertion of a solo long terminal repeat (LTR) of the ecotropic murine leukemia virus in the reverse orientation in the intron of the mdr-3 gene, causing abnormal splicing and thereby disrupting the mdr-3 gene function. In addition, histopathological analysis of the brains of the ivermectin-treated mutants revealed selective neuronal degeneration in the hippocampal CA3 region. This is the first reported case of a gene mutation induced by a solo retroviral LTR with a phenotypic consequence in the mouse, and may provide new insights into the understanding of the effects of viral solo LTR sequences on mammalian gene expression. |
