Gandolfi B, Gruffydd-Jones TJ, Malik R, et al. First WNK4-hypokalemia animal model identified by genome-wide association in Burmese cats. PLoS ONE. 2012; 7: e53173. [Free, full text article]
Potassium is an important cation required for establishing normal cell resting membrane potential and for normal cell excitability in all mammals. Generalized or localized episodic or persistent muscle weakness can occur due to low potassium levels secondary to low dietary potassium intake or abnormal metabolism or elimination of potassium caused by disease. Low potassium can also result from inherited defects and previous genetic studies have identified heritable syndromes of muscle weakness in humans, horses, and non-USA Burmese cats. Burmese hypokalemia periodic polymyopathy is thought to be an autosomal recessive condition characterized by episodic or constant muscle pain from palpation, generalized muscle weakness, or local muscle weakness evidenced by ventroflexion of the head and neck and head bobbing, stilted or crouched gait, dorsal scapulae protrusion, and muscle tremors. The disease usually becomes evident in kittens at 2 to 6 months of age, or rarely up to 2 years old.
Researchers from University of California, Davis and collaborators used performed a genome-wide association study to localize the gene responsible for hypokalemic periodic polymyopathy in non-USA Burmese breed. Thirty-five affected Burmese cats and 25 unaffected Burmese cats were identified from Australia, UK, and Germany and their DNA was used in the genetic case-control study. A significant association was identified on feline chromosome E1, and a mutation discovered in the WNK4 gene. All affected cats were homozygous for the mutation. The mutation causes a premature stop codon resulting in a truncation of the C-terminal coiled coil domain and the loss of its phosphorylation site. WNK4 is a serine-threonine protein kinase that is virtually exclusively expressed in the kidneys and is involved in salt, water, potassium, and pH homeostasis. WNK kinases have also recently been recognized to comprise a signalling pathway essential for normal development, regulation of arterial pressure, normal electrolyte balance, and for sensory nerve function. It is postulated that the mechanism causing hypokalemia in Burmese cats may involve a potassium-losing nephropathy. The researchers also developed a genetic test for identification of carrier cats prior to mating, and thus avoid propagation of the mutated gene. [GO]
Funding: This project was partially funded by the Cat Health Network grant D12FE-508.
See also: Mason K. A hereditary disease in Burmese cats manifested as an episodic weakness with head nodding and neck ventroflexion. J Am Anim Hosp Assoc. 1988; 24: 147-51.