Study of spontaneous hypokalemic polymyopathy in Felis catus in comparison with thyrotoxic periodic paralysis in humans: cloning and searching for mutations in its orthologue gene KCNJ18

• Grant number: 12/02529-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: July 01, 2012
• End date: May 31, 2013
• Field of knowledge: Biological Sciences - Genetics - Animal Genetics
• Principal Investigator: Magnus Régios Dias da Silva
• Grantee: Marlyn Zapata Montoya
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Thyrotoxic Periodic Paralysis (TPP) is the clinical condition characterized by sudden and reversible loss of muscle strength associated with thyrotoxicosis and hypokalemia. TPP is the most frequent of acquired acute flaccid paralysis in young male and is more prevalent in Asian and Latin American population. We have recently known that TPP is the newest form of endocrine channelopathy comprising a group of periodic paralysis. We believe that susceptibility to TPP in humans is multigenic (genetic heterogenity) in which only subset thyrotoxic patients with mutation develop paralysis. Up on an international collaboration we have identified a new Kir paralogue gene, which was named KCNJ18 (channel Kir2.6) and also found four different mutations. Clinical presentation of TPP in humans is similar to the hypokalemic polymiopathy in cats. In this way, seven months ago, we started studying the molecular aspects that may cause the susceptibility to paralysis in the hyperthyroid cat; including its etiology, epidemiology, differential diagnosis and clinical manifestations, physiopathology and treatment. To understand the spontaneous animal model of hypokalemic myopathy that happens in the cat, we propose to clone an ortologue gene in the cats (similar to human KCNJ18) and search for mutations associated to TPP; as well as other ortologues genes of the family Kir2.x. In association with endocrinology veterinary will also study the clinical prevalence of hipocalemic and flaccid paralysis in hyperthyroid cats. With this feline animal model of TPP, we aim to clone the ortologue Kir2.6 channel and confirm that the inherence pattern including those hyperthyroid cats susceptible to periodic muscle weakness and/or cervical ventroflexion, symptoms that resemble those from TPP in humans. After to gene and mutations will be identified, we will follow through in vitro study by inducing thyrotoxicosis in Feline Skeletal Muscle Cells (FSkMC) and verifying Kir2.x gene expression.