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Hyperuricosurie is a disease characterised by excessive excretion of uric acid into the urine, leading to formation of uric acid stones.
Allantoin is the end product of purine catabolism in all mammals with the exception of man, apes and Dalmatian dog breed. Man and Dalmatian dogs produce uric acid resulting in increase of uric acid concentration in blood and urine and can cause serious health problems. However, the mechanism of production of high levels of uric acid concentration in blood is different in both kinds.
In kidneys of man and apes, the uric acid is filtrated in glomeruli and part of it is reabsorbed in proximal tubules, where it enters again into the circulation. During the evolution of primates, several nonsense mutations of uratoxidase enzyme were substituted (catalyses the enzymatic oxidation of uric acid to allantoin), which led to suppression of enzyme function and to increase in concentration of uric acid in blood and urine. The uric acid circulates as free uric acid or uric acid salts in plasma, where it serves as free radical. The uric acid predisposes the man to uric acid stone formation and gout.
The Dalmatian dog breed has lost the ability of reabsorption of uric acid in the proximal tubule thanks to mutation in urate transport protein; the excretion of uric acid equals to or exceeds the rate of glomerular filtration. In Dalmatians, a defect in urine metabolism caused that the Dalmatians excrete the uric acid instead of allantoin. The uric acid forms uric acid stones in Dalmatians. This trait was probably fixed in the breed through selection for a more distinctive spotting pattern. The specific pattern of their coat has been created by at least three various mutations: 1) a mutation for white coat colour (MITF gene, Karlsson et al. 2007), 2) a dominant mutation at the T-locus causing spotting (Little 1957), 3) a mutation influencing the spot size - just with this mutation is probably segregated the mutation responsible for the occurrence of hyperuricosuria (Schaible 1976).
Hyperuricosuria in dogs is caused by single nucleotide exchange of c.G563T (p.C188F) in SLC2A9 gene (gene for urate transport) (Bannasch et al. 2008). Hyperuricosuria is an autosomal recessive inherited disease. That means that the disease will develop only in dogs that inherited the mutation from both parents - these individuals are called affected homozygotes. Individuals with only one mutated allele are carriers of the disease without clinical symptoms.
All dogs of Dalmatian breed are affected by hyperuricosuria; all dogs of Dalmatian breed are affected homozygotes - they have mutated both alleles of SLC2A9 gene. The same mutation has also been found in the breeds such as Bulldog, Black Russian Terrier, American Staffordshire Terrier, Retriever, Parson Russell Terrier, South African Boerboel, Waimaraner, Big Munsterland Pointer, German shepherd; occurrence in other dog breed is not excluded (Karmi et. al 2010).

N. Karmi, E.A. Brown, S.S. Hughes, B. McLaughlin, C.S. Mellersh, V. Biourge, and D.L. Bannasch: Estimated Frequency of the Canine Hyperuricosuria Mutation in Different Dog Breeds; J Vet Intern Med 2010;24:1337-1342
Karlsson EK, Baranowska I, Wade CM, Salmon Hillbertz NH, Zody MC, et al. (2007) Efficient mapping of mendelian traits in dogs through genome-wide association. Nat Genet 39: 1321-1328.
Little C (1957) The Inheritance of coat color in dogs. New York: Howell Book House. 194 p.
Schaible R (1976) Linkage of a pigmentary trait with a high level of uric acid excretion in the Dalmatian dog. Genetics 83: S68.
Bannasch D, Safra N, Young A, Karmi N, Schaible RS, et al. (2008) Mutations in the SLC2A9 Gene Cause Hyperuricosuria and Hyperuricemia in the Dog. PLoS Genet 4(11): e1000246. doi:10.1371/journal.pgen.1000246

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