| First Author | Tufarelli C | Year | 1998 |
| Journal | Dev Biol | Volume | 200 |
| Issue | 1 | Pages | 69-81 |
| PubMed ID | 9698457 | Mgi Jnum | J:49157 |
| Mgi Id | MGI:1276787 | Doi | 10.1006/dbio.1998.8950 |
| Citation | Tufarelli C, et al. (1998) Hair defects and pup loss in mice with targeted deletion of the first cut repeat domain of the Cux/CDP homeoprotein gene. Dev Biol 200(1):69-81 |
| abstractText | CDP, a ubiquitous homeoprotein homologous to Drosophila cut, is implicated as a transcriptional repressor in several developmental systems. It contains four independent DNA binding domains: three ''cut repeats'' plus the homeodomain. The murine Cux/CDP gene spans more than 200 kb and is composed of at least 21 exons. We designed a targeting construct to replace the first cut repeat with a neomycin resistance cassette, introducing a nonsense mutation after position 1319 of the 4.5-kb reading frame of Cux/CDP. We expected to generate a truncated product of approximate to 60 kDa with this construct, but instead rye obtained mice expressing a mutant form of the protein, with an internal deletion of 246 amino acids encompassing cut repeat 1, but intact in the C-terminal region. Ribonuclease protection assays and direct sequencing of mutant cDNA obtained by RT-PCR demonstrate skipping of exons 10 and 11 in the mutant. Homozygous mutant mice, designated Cux/CDP Delta CR1, display a phenotype characterized by curly vibrissae and wavy hair. We also observed a high degree of pup loss in litters born to mutant females, most likely on a nutritional basis. The mutant protein is present at levels slightly greater than wild-type, but exhibits the same tissue distribution as wild-type protein, and has approximately normal affinity for known target sequences (though no DNA targets identified to date require the first cut repeat for binding). These results support the hypothesis that the different DNA binding domains of the ubiquitous Cux/CDP protein are responsible for regulation of different genes in diverse tissues during development. (C) 1998 Academic Press. |
