The Domestic Cat, Felis catus, as a Model of Hereditary and Infectious Disease

Abstract

The domestic cat, currently the most frequent of companion animals, has enjoyed a medical surveillance, as a nonprimate species, second only to the dog. With over 200 hereditary disease pathologies reported in the cat, the clinical and physiological study of these feline hereditary diseases provides a strong comparative medicine opportunity for prevention, diagnostics, and treatment studies in a laboratory setting. Causal mutations have been characterized in 19 felid genes, with the largest representation from lysosomal storage enzyme disorders. Corrective therapeutic strategies for several disorders have been proposed and examined in the cat, including enzyme replacement, heterologous bone marrow transplantation, and substrate reduction therapy. Genomics tools developed in the cat, including the recent completion of the 2-fold whole genome sequence of the cat and genome browser, radiation hybrid map of 1793 integrated coding and microsatellite loci, a 5-cM genetic linkage map, arrayed BAC libraries, and flow sorted chromosomes, are providing resources that are being utilized in mapping and characterization of genes of interest. A recent report of the mapping and characterization of a novel causative gene for feline spinal muscular atrophy marked the first identification of a disease gene purely from positional reasoning. With the development of genomic resources in the cat and the application of complementary comparative tools developed in other species, the domestic cat is emerging as a promising resource of phenotypically defined genetic variation of biomedical significance. Additionally, the cat has provided several useful models for infectious disease. These include feline leukemia and feline sarcoma virus, feline coronavirus, and Type C retroviruses that interact with cellular oncogenes to induce leukemia, lymphoma, and sarcoma.