As the genomes of both humans and the mouse are now roughly complete, we now face the daunting task of determining the functions of all of the various genes in the genome. Functional analysis of the mouse genome via large-scale mutagenesis has provided numerous new autosomal mutations, but X-linked phenotypes have been largely underrepresented in these screens. Here, I propose a mutagenesis project with a novel breeding scheme to detect X-linked recessive phenotypes. Male mice will be mutagenized with the chemical mutagen END and then bred to female mice that have only one X chromosome. (Unlike human females with only one X chromosome, mice with this condition are fertile.) Half of the female mice that result from this cross will receive a mutagenized X chromosome from their father and no sex chromosome from their mother. These mice will therefore be hemizygous females and will express any viable X-linked recessive phenotype that was induced by the mutagenesis. Mutant mice will be identified by a thorough phenotype screen and will be bred to determine heritability and X-linkage of the mutant phenotype. X-linked recessive mutations will then be cloned by traditional mapping and positional cloning techniques.
| Probst, Frank J; Cooper, Mitchell Lance; Cheung, Sau Wai et al. (2008) Genotype, phenotype, and karyotype correlation in the XO mouse model of Turner Syndrome. J Hered 99:512-7 |
| Probst, Frank J; Roeder, Elizabeth R; Enciso, Victoria B et al. (2007) Chromosomal microarray analysis (CMA) detects a large X chromosome deletion including FMR1, FMR2, and IDS in a female patient with mental retardation. Am J Med Genet A 143A:1358-65 |
