Understanding hereditary diseases using the dog and human as companion model systems

Abstract

Animal models are requisite for genetic dissection of, and improved treatment regimens for, human hereditary diseases. While several animals have been used in academic and industrial research, the primary model for dissection of hereditary diseases has been the many strains of the laboratory mouse. However, given its greater (than the mouse) genetic similarity to the human, high number of naturally occurring hereditary diseases, unique population structure, and the availability of the complete genome sequence, the purebred dog has emerged as a powerful model for study of diseases. The major advantage the dog provides is that it is afflicted with approximately 450 hereditary diseases, about half of which have remarkable clinical similarities to corresponding diseases of the human. In addition, humankind has a strong desire to cure diseases of the dog so these two facts make the dog an ideal clinical and genetic model. This review highlights several of these shared hereditary diseases. Specifically, the canine models discussed herein have played important roles in identification of causative genes and/or have been utilized in novel therapeutic approaches of interest to the dog and human.

Fig. 1

A Hound/Labrador retriever colony having XLHN is maintained at Texas A&M University. A A carrier female (left) can live up to seven years. An affected male (right) will enter renal failure before two years of age. B Immunofluorescent staining for COL4A5 in glomeruli of a normal dog. C Immunofluorescent staining for COL4A5 in glomeruli of an affected dog showing complete lack of labeling. Glomeruli images taken with permission from Am J Vet Res (1999) 60(3):373–383