Genetic basis - This type of cystinuria in Labrador Retrievers is caused by a frameshift mutation, a single base pair deletion in the SLC3A1 gene (c.350delG) located in exon 1. The deletion causes a frameshift leading to a premature stop codon (p.Gly117Alafs*41), truncating the rBAT protein encoded by SLC3A1 from 784 amino acids to only 157 amino acids. The mutation is inherited as an autosomal recessive trait, meaning dogs must inherit two copies of the mutated gene to be affected.
Pathophysiology - The SLC3A1 gene encodes the rBAT protein, part of the b0,+ amino acid transporter complex responsible for reabsorption of cystine and other dibasic amino acids in the kidneys. The truncated rBAT protein caused by this mutation is likely unstable, unable to dimerize, and nonfunctional, causing defective cystine transport. This defective transporter leads to increased urinary excretion of cystine, which precipitates as crystals and forms cystine stones (uroliths) in the urinary tract.
Complications - Affected dogs develop cystine urolithiasis, which can cause urinary obstruction, pain, infections, hematuria, and potentially kidney damage. Both male and female Labrador Retrievers can be affected; males tend to develop stones earlier due to anatomical differences in the urinary tract. Some dogs may develop nephrolithiasis (kidney stones) as well as bladder stones.
Why This Matters to Breeders and Vets - Genetic testing enables identification of carriers and affected dogs for informed breeding decisions to reduce the incidence of cystinuria. Early diagnosis and management are important in affected dogs to prevent urinary obstruction and associated complications. Awareness of the genetic basis helps veterinarians diagnose and manage cystinuria more effectively.