A comparative genetic approach for the investigation of ageing grey horse melanoma

Ageing grey horses are particularly susceptible to melanoma. Using segregat ion analysis, six genetic and nongeneric (environmental) models in two grey horse family groups (n = 71) were compared. The polygenic model still fits the data significantly better than an environmental model, indicating a st rong genetic impact on the phenomenon. Pmel17/gp100 and TYRP1/gp75, two gen es which are specific for melanocytes, and Cdkn2a/p16 a gene coding tor an inhibitor of a cell cycle regulator were partially cloned, sequenced and ma pped. Using Northern blotting analysis a striking difference in mRNA expres sion of Pmel17/gp100 and TYRP1/gp75 was found comparing skin samples of sol id-coloured (normal level) and grey horses (low level) as well as horse mel anoma tumour samples thigh). Staining of skin samples with antibodies recog nizing the product of Pmel17/gp100, confirmed the results of the correspond ing Northern blotting analysis. It seems that Pmel17/gp100 and TYRP1/gp75 a re involved in progressive greying of horses. No mutation was found in a pa rtial sequence of equine Cdkn2a/p16 analysed so far. Thus, the relation bet ween equine melanoma susceptibility and Cdkn2a/p16 is subject to further in vestigation.