Uric Acid Metabolism
The Gene for Uric Acid Metabolism
The canine digestive system has evolved so that certain proteins called purines are metabolised into uric acid. Uric acid is then converted into allantoin which is excreted without harm. The gene responsible for doing this is SLC2A9.
Dalmatians & High Uric Acid (HUA)
In the Dalmatian, SLC2A9 has undergone a mutation and no longer functions. Uric acid is not converted into harmless allantoin. Instead it accumulates in the urinary tract, most notably the bladder, and creates a condition known as hyperuricosuria in which the level of uric acid is so high that it may form urate crystals. The mutation that causes this is called the HUA (or High Uric Acid) gene.
Dogs with a copy of the non-mutated, normal (NUA) gene only form urate stones and crystals when their uric acid levels are raised by unusual circumstances such as liver shunts or reactions to certain medications.
Inheritance of Genes
All dogs have two copies of SLC2A9. The NUA (or Normal Uric Acid) version is dominant(U), and the mutant HUA gene is recessive(u), as such a dog only has to inherit one copy of the NUA gene in order to be able to process purines normally. The possible combinations and their effect on uric acid levels are as follows:
| Genes inherited | Uric acid levels in bladder |
| NUA/NUA (UU) | Uric acid metabolised = Low Uric Acid Levels |
| NUA/HUA (Uu) | Uric acid metabolised = Low Uric Acid Levels |
| HUA/HUA (uu) | Uric acid not metabolised = High Uric Acid Levels |
This is the same way that the recessive gene for liver spotting (b) works. Two copies of bb are necessary for a liver Dalmatian. Bb or BB results in a black-spotted Dalmatian.
Dalmatians
Although some Bulldogs and Russian Black Terriers carry the mutant gene, many also carry the NUA version. By using genetic testing to select appropriate sires and dams, these breeders can ensure that all the pups they produce have normal uric acid levels.
This was not the case for Dalmatians. Back in 1938, scientists determined that ALL Dalmatians carried two copies of the HUA gene and were susceptible to forming urate stones and crystals.
We were unlucky that an important gene for spotting was situated next to the HUA gene, and genes next to each other tend to be inherited together. As past breeders selected for better spots, they unknowingly also selected for high levels of uric acid.
Thus, the backcross project was initiated in order to reintroduce the dominant NUA gene. For details 'Click Here'
