International Mammalian Genome Society

The 13th International Mouse Genome Conference
October 31-November 3, 1999

Table of Contents * Structure * Bioinformatics * Sequence * Mapping * New Tools * Gene Discovery * Developmental * Mutagenesis * Functional Genomics

F11 Progress Towards the High Resolution Mapping of nackt: A Novel Mouse Mutation Affecting Hair Growth and CD4+ T Cells Development

Fernando Benavides1, Natalia Martin Palenzuela2, Jean Jaubert2, Jean-Louis Guénet2, Claudio J. Conti1. 1The University of Texas M.D. Anderson Cancer Center, Science Park-Research Division, Smithville, Texas 78957, USA.; 2Unité de Génétique des Mammifères, Institut Pasteur, 75724 Paris cedex 15, France

We have recently reported a new mouse mutation (nackt) affecting the skin and associated with CD4 deficiency (Immunogenetics 49: 413-419, 1999). We determined that nackt is an autosomal recessive mutation and we mapped to mouse chromosome 13, 30 to 40 cM distal from the centromere. This region with homology with human chromosome 5q and 9q. The affected animals show growth retardation and diffuse alopecia. The most striking immunological finding is a marked decrease in the proportion of CD4+ T cells in lymphoid tissues. When homozygous nackt mice are bred in a conventional environment, with enzootic Mouse Hepatitis Virus (MHV) infection, growth is much retarded and the affected animals developed a wasting syndrome and dermatitis. Histopathologic studies reveal hepatitis and thymic atrophy suggesting an immunodeficiency of the mutant mice against natural MHV infection.

We now report genotyping of 100 intersubspecific F2 mice to further define the critical region for the positional cloning of the gene. These results narrow down the segment of chromosome 13 containing nackt to a 2-cM interval between D13Mit23 and D13Mit281 and eliminate several genes as candidates for the nackt mutation. Within this 2 cM region, we found a 1-cM congenic region whose microsatellites markers (D13Mit 7, 39, 43, 142, 311, 50, 283, 209, 223 and 253) show allele sizes different from the inbred strains used in our crosses. Presumably, this small segment derives from the unknown outbred stock where the nackt mutant allele arose. The nackt mutation represents another mutation with pleiotropic effects on the skin and the immune system. It is likely that the nackt mutation will be an useful tool to study the selection mechanisms operating in the thymus and also as an animal model for AIDS-like immunodeficiencies and dermatitis.


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