ADPKD
Inherited
Fluid filled cysts in kidney and occasionally liver and pancreas
Deterioration in renal function due to compression of the renal parenchyma
Heterozygous variant located in the PKD1 gene with a nonsense single nucleotide polymorphism in exon 29 (chrE3:g.42858112C>A, the conventional PKD1 variant).
This variant causes a stop codon, truncating the protein up to 25% at the c-terminus
Homozygous lethal in the embryonic stage
PKD1 encodes polycystin 1 (PC1), which is a membrane-bound large multi-domain glycoprotein with a G protein couples receptor proteolytic site
Physiological function is unclear; located on the primary cilia , a flagellar organelle protruding from the cell surface used for mechanotransduction
PC1 I s thought to perform an important role in transmitting signals from outside the cell
The loss of functional PC1 appears to contribute to the cystogenesis n ADPKD and much research has been conducted to identify the underlying mechanisms
Proposed the influence of various upregulated or down regulated intracellular signals while others have said that macrophage recruitment by the primary cilia plays a huge role in cytogenesis
2 models of the relationship between PC1 dsage and cystogenesis have been established
2 - hit model :After inactivation of one allele by germiline mutation , a somatic mutation occurs , inactiviating the other allele and thereby causing cystogenesis
Threshold theory : more recent suggests that the disease occurs when the PC1 levels drop below a certain threshold and do not necc, have to be at zero
Since the variant responsible for the feline ADPKD truncates PC1 it can be assumed that the truncated abnormal protein is unable to function properly , leading to a lack of functional PC1
Genetic tests to identify the PKD1 gene but cant predict the severity of disease or evaluate progression
Persian and related breeds
In Japan also seen in Scottish folds and American SHorthiar
Prevenlence in few studies reported as 13.5% in China, 33% in Slovenia 40$ in Japan -> mostly focused on persian cats or cats suspected of CKD - small numbers of cats
No data on cat population as a whole regarding prevalence of the disease or the PKD1 gene
Some studies have revealed that cats without the conventional PKD1 variant can develop ADPKD - suggests that an unknown variant may severe as another cause of ADPKD
