Canine Cystinuria (CY) is an autosomal recessive disorder that affects a dog's ability to filter cysteine out of urine. Autosomal recessive disorders are disorders that can be passed from either parent and require two copies of the gene to show symptoms. Cysteine is a substrate that helps transport nutrients throughout the body. CY is characterized by the inability to filter cysteine from the urine, which causes painful blockages and kidney stones.
Normally tubules in the kidney are responsible for the re-absorption of cysteine, filtering it out through the urine. In dogs with Canine Cystinuria, the tubules are unable to transport the cysteine, allowing it to accumulate in the urine. Cysteine is generally insoluble in the acidic conditions of canine urine, allowing it to crystallize and form caliculi, also known as stones.
Not every dog that has the mutation responsible for Cystinuria will exhibit symptoms. Stones causing inflammation and blockage are often more common in males. This is due to their long, narrow urethra. Females exhibit symptoms much less frequently and may be completely asymptomatic.
Canine Cystinuria affects over 60 breeds of dogs. Research suggests that Newfoundlands carry a more severe form of this disease than other breeds. In a variety of breeds affected by Canine Cystinuria, symptoms are often not experienced until about 4-5 years in age. However, Newfoundlands may begin experiencing problems as early as 6 months to one year of age. Newfoundlands are much more likely to experience recurring urethral blockages that could require surgical intervention.
In the Newfoundland breed, the cause of Cystinuria is a single nucleotide polymorphism that occurs in the SLC3A1 gene (a gene that produces the transport protein). The polymorphism causes a premature stop codon in the DNA, thus causing an error in protein production. This error in the DNA leads to Cystinuria.
Cystinuria is a recessive disorder, meaning that the dog must have two copies of the defective gene to suffer from the disease. Because Cystinuria is a recessive disorder, a dog can also be a carrier of this disease. This means that a dog carries one copy of the mutation, but does not display any symptoms. A carrier dog can pass on this mutation to their offspring and if they mate with another carrier dog, can produce offspring affected by Cystinuria.
|CY/CY||Dog carries two copies of the mutation associated with Cystinuria, and will be affected.|
|n/CY||Dog carries one copy of the mutation associated with Cystinuria.|
|n/n||Dog is negative for the mutation associated with Cystinuria.|
Henthorn PS, Liu J, Gidalevich T, Fang J, Casal ML, Patterson DF, Giger U. Canine cystinuria: polymorphism in the canine SLC3A1 gene and identification of a nonsense mutation in cystinuric Newfoundland dogs. Hum Genet. 2000 Oct; 107(4):295-303. [PubMed: 11129328]