The prevalence rate for cardiovascular malformations in dogs presented to a large university veterinary clinic was 6.8 per 1000. Patent ductus arteriosus, as in man, was found predominantly in females. Breed-specific prevalence rates were significantly greater in purebred dogs than in mongrels, and the breed distributions of patent ductus arteriosus, pulmonic stenosis, subaortic stenosis, persistent right aortic arch, and tetralogy of Fallot were significantly different than would be expected if all breeds were equally susceptible to each type of malformation. On the basis of these observations, two hypotheses were made: (1) Genetic factors are determinants of certain types of congenital heart disease in the dog. (2) These genetic factors have specific effects on cardiac morphogenesis, resulting in specific types of cardiovascular malformations. Preliminary genetic studies confirmed the specific hereditary transmission of valvular pulmonic stenosis in beagles, persistent right aortic arch in German shepherds, and conal septal defects (including ventricular septal defects and tetralogy of Fallot) in keeshonden. The pattern of inheritance of these defects was not consistent with any simple genetic hypothesis. Patent ductus arteriosus in dogs of poodle ancestry and fibrous subaortic stenosis in Newfoundlands were shown provisionally to be transmitted in a manner consistent with autosomal dominant inheritance. The significance of these findings is considered in relation to present and future understanding of the etiology and pathogenesis of congenital heart disease.

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Breeding studies in a strain of miniature schnauzer dogs with Persistent Müllerian Duct Syndrome (PMDS) indicate this syndrome is inherited as an autosomal recessive trait, as it is in man. Testes of neonatal dogs affected with PMDS and normal male littermates were examined for Müllerian Inhibiting Substance (MIS) production by immunohistochemistry and bioassay. MIS immunoactivity was detected in Sertoli cells of normal and affected pups using an avidin-biotin complex-enhanced method. Rat embryonic Müllerian ducts regressed when cocultured with testis fragments of both normal and affected pups in a graded organ culture bioassay, demonstrating that the MIS produced was bioactive. These findings indicate that Müllerian duct persistence in affected dogs is not due to a mutation in the structural gene for MIS, but rather, by inference, to a failure of response to MIS at the receptor level.

The relationships between body size, growth hormone (GH) secretory capacity and circulating insulinlike growth factor I (IGF I) levels were studied in genetically-determined subgroups of disparate size within one breed of dogs, the Poodle. Standard (large) Poodles exhibited six times the mean plasma IGF I concentration found in Toy Poodles. The mean IGF I level found in Standard Poodles significantly differed from the one found in Miniature and Toy Poodles (P < 0.001). The correlation between circulating IGF I levels and body size was found to be highly significant (P < 0.001; r = 0.88). All dogs secreted similar, normal amounts of GH in response to clonidine administration.The results show that body weight is correlated with IGF I levels rather than with the GH secretory capacity, thus providing indirect evidence for IGF I as an important in vivo growth-promoting principle.

Polycystic kidney and liver disease was present in four of six female and three of five male offspring born in two matings between the same pair of West Highland White Terriers. Clinical signs were apparent and serum biochemistry analysis consistent with liver failure was evident by 5 weeks of age. Affected pups were euthanatized because of their disease. Renal cysts were confirmed to be of collecting duct origin by Dolichos bifluros agglutinin lectin histochemistry, and hepatic cysts were of biliary origin. The clinically unaffected parents were related through multiple common ancestors, and there were no reports of similar disease in related dogs. An autosomal recessive mode of inheritance is therefore suggested. This is the first report of polycystic kidney and liver disease in the West Highland White Terrier. The features of the disease in these pups are similar to those of autosomal recessive polycystic kidney disease (ARPKD) in humans. The West Highland White Terrier may therefore be a potential animal model for ARPKD.