FN - Familiar nephropathy, test for English Cocker Spaniels

A genetic examination for English Cocker Spaniels. For the analysis a blood probe is required - 1 ml of blood sample in the anticoagulant EDTA.

The Familiar Nephropathy is an inherited disease causing kidney failure in English Cocker Spaniels. The disease is caused by molecular abnormalities of collagens in capillaries, where the blood is filtrated in kidneys. The symptoms of FN are similar to those of Alport syndrome in humans. (Lees et al. 1997).

Glomerular capillary walls consist of outer, inner and a middle layer also called the glomecular basement membrane (GBM). The GBM is built of a network of type IV collagen molecules that is necessary to maintain normal structure and function of the glomerular capillary walls. The type IV collagen is an assembly of three distinct peptide chains and each of these peptide chains is encoded by separate gene. A mutation in any one of these three genes can disrupt the molecular integrity of the entire collagen IV network in the GBM and cause progressive renal damage that leads to kidney failure. In English Cocker Spaniels affected by FN, the peptide products of two genes COL4A3 and COL4A4U encoding the peptides of type IV collagen contained in GBM are completely absent (Gubler et al. 1995, Lees et al. 1998b).

In connection with the FN disease in English Cocker Spaniels, one-point substitution of adenine for thymine in position 115 in exon 3 of COL4A4-gene has been described (mutation c.115A˃T), and this mutation results in creation of premature stop codon (Davidson et al. 2006).

Dogs with FN develop chronic renal failure usually between 6 months and 2 years of age. The first clinical signs observed include excessive water consumption, excessive urine volume, reduced growth rate or weight loss, poor quality hair coat, reduced appetite and vomiting.

FN in English Cocker Spaniels is an autosomal recessively inherited disease and it means that the disease develops only in individuals, which inherited from their parents both mutant alleles (P/P - positive/positive - m mutant homozygote). An individual, which inherits the mutant allele from one parent (result N/P - negative/positive) is heterozygous and a carrier of the disease; this individual transfers this mutant allele to its offsprings. If both parents are heterozygous (carriers of FN), then theoretically, 25 % of the puppies born will be affected.

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References:

Lees, G.E., R.G. Helman, C.E. Kashtan, A.F. Michael, L.D. Homco, N.J. Millichamp, Y. Ninomiya, Y. Sado, I. Naito, and Y. Kim. 1998b. A Model of autosomal recessive alport-syndrome in english cocker spaniel dogs. Kidney International. 54:706-719.

Lees, G.E., P.D. Wilson, R.G. Helman, L.D. Homco, and M.S. Frey. 1997. Glomerular ultrastructural findings similar to hereditary nephritis in 4 English cocker spaniels. Journal of Veterinary Internal Medicine. 11:80-5.

Gubler, M.C., B. Knebelmann, A. Beziau, M. Broyer, Y. Pirson, F. Haddoum, M.M. Kleppel, and C. Antignac. 1995. Autosomal recessive Alport syndrome: immunohistochemical study of type IV collagen chain distribution. Kidney International. 47:1142-7.

Davidson AG, Bell RJ, Lees GE, Kashtan CE, Davidson GS, Murphy KE. Genetic cause of autosomal recessive hereditary nephropathy in the English Cocker Spaniel. Journal of Veterinary Internal Medicine. 21(3):364-6