Genetic basis - This type of cystinuria in Australian Cattle Dogs is caused by an in-frame 6 base pair deletion (c.1095_1100delACCACC) in the SLC3A1 gene. The deletion removes two threonine amino acids (p.Thr366_Thr367del) in the rBAT protein encoded by SLC3A1, which is part of the cystine transporter in kidney cells. The condition is inherited as an autosomal dominant trait, meaning that only one copy of the mutated gene is needed to cause cystinuria.
Pathophysiology - The SLC3A1 gene encodes the rBAT protein, a subunit of the b0,+ amino acid transporter responsible for reabsorption of cystine and other basic amino acids in the kidney tubules. The deletion occurs in a highly conserved extracellular domain important for substrate trafficking, likely impairing normal cystine transport function. Impaired transporter function leads to increased cystine concentration in the urine, which is poorly soluble, causing cystine crystal and stone formation.
Complications - Cystine crystals or urolithiasis in the urinary tract, potentially leading to urinary obstruction, pain, infections, and kidney damage if untreated. Male dogs tend to have a higher risk for urinary obstruction due to anatomical differences in the urethra. Homozygous dogs (two copies of the mutation) have more severe clinical signs and earlier onset of symptoms compared to heterozygous (one copy) dogs.
Why This Matters to Breeders and Vets - Autosomal dominant inheritance means affected dogs can pass the mutation to approximately 50% of their offspring, increasing disease risk in the breed. Genetic testing enables identification of affected and carrier dogs to facilitate informed breeding decisions. Vets benefit from knowledge of this condition for early diagnosis, treatment, and managing urinary health in affected dogs.
