| First Author | Kudoh H | Year | 2005 |
| Journal | Biochem Biophys Res Commun | Volume | 328 |
| Issue | 2 | Pages | 507-16 |
| PubMed ID | 15694376 | Mgi Jnum | J:96210 |
| Mgi Id | MGI:3529711 | Doi | 10.1016/j.bbrc.2004.12.191 |
| Citation | Kudoh H, et al. (2005) A new model mouse for Duchenne muscular dystrophy produced by 2.4Mb deletion of dystrophin gene using Cre-loxP recombination system. Biochem Biophys Res Commun 328(2):507-16 |
| abstractText | Duchenne muscular dystrophy (DMD) is caused by mutation in the 2.4-Mb dystrophin (DMD) gene . This gene encodes a number of tissue-specific isoforms of dystrophin generated by transcription from at least seven promoters and also by alternative splicing. We deleted entire genomic region of the DMD gene on mouse chromosome X using a Cre-loxP recombination system. Introduction of a loxP site in dystrophin's first and last exon by homologous recombination in mouse embryonic stem (ES) cells generated 'DMD-floxed' (flanked by loxP sites) ES cells, which we subjected to Cre-mediated excision leading to establishment of 'DMD-null' ES cell lines. The DMD-null mice produced from the DMD-null ES cells were viable but displayed severe muscular hypertrophy and dystrophy. In addition to the muscular impairment, the DMD-null mouse exhibited some behavioral abnormality and male sterility. The DMD-floxed mice produced from the DMD-floxed ES cells were viable, phenotypically normal, and were born with the expected Mendelian frequency, despite the absence of brain (cortical)-type dystrophin (Dp427c) expression. Since production of multiple dystrophin isoforms due to alternative splicing or exon skipping is totally prevented in the DMD-null mouse, these new mutants will provide an improved model system for functional studies of dystrophin and its isoforms. |
