Testing of dogs: AMPn

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Polyneuropathy in Alaskan Malamute

AMPN (Polyneuropathy in Alaskan Malamute) is one of the several canine hereditary neuropathies described in 22 dog breeds that are similar to the human CMT (Charcot-Marie-Tooth syndrome). The occurrence of polyneuropathy in the population of Alaskan malamute was first described in 1970. For example in Scandinavia, the disease was considered eradicated through breeding programmes, but during the last years, new cases of this disease have been recorded in the Nordic countries, the USA and others.

The onset of clinical signs starts between 3 to 19 months of age. The affected dogs first have noisy breathing and in some case in combination with paraperesis. The affected dogs may suffer only from paraperesis and gradually other typical neurological signs may occur - exercise intolerance, gait abnormalities, inspiratory stridor (harsh sound when breathing in), gait abnormalities may progress to paraparesis and muscle weakness of all four extremities (so-called bunny-hopping gait).In the Alaskan Malamute breed, the point mutation c.293G˃T in the NDRG1 gene in exon 4 causing a p.Gly98Val amino-acid substitution (Bruun et al., 2013) was described as the causative mutation. The protein encoded by NDGR1 gene is a cytoplasmic protein participating in stress-affecting reactions, hormone reactions, cell growth and their differentiation (Drögemüller et al, 2010). In affected dogs, the function of the NDRG1 protein changes and the signs of polyneuropathy occur (Bruun et al., 2013).

Mutation that causes Polyneuropathy in Alaskan Malamute is inherited as an autosomal recessive trait. That means the disease affects dogs with P/P (positive / positive) genotype only. The dogs with P/N (positive /negative) genotype are clinically without any symptom. They are genetically considered carriers of the disease (heterozygotes). In offspring of two heterozygous animals following genotype distribution can be expected: 25 % N/N (healthy non-carriers), 25 % P/P (affected), and 50 % N/P (healthy carriers). Because of high risk of producing affected offspring, mating of two N/P animals (carriers) can not be recommended.

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References:

Drögemüller C et al. A Deletion in the N-Myc Downstream Regulated Gene 1 (NDRG1)Gene in Greyhounds with Polyneuropathy PLoS One. 2010 Jun 22;5(6):e11258.

Bruun CS, Jäderlund KH, Berendt M, Jensen KB, Spodsberg EH, et al. (2013) A Gly98Val Mutation in the N-Myc Downstream Regulated Gene 1 (NDRG1) in Alaskan Malamutes with Polyneuropathy. PLoS ONE 8(2): e54547. doi:10.1371/journal.pone.0054547

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Usual turnaround time: 7 business days
1 test price: 45.00 $ without VAT