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

Ageing grey horses are particularly susceptible to melanoma. Using segregation analysis, six genetic and nongenetic (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 strong genetic impact on the phenomenon. Pmel17/gp100 and TYRP1/gp75, two genes which are specific for melanocytes, and Cdkn2a/p16 a gene coding for an inhibitor of a cell cycle regulator were partially cloned, sequenced and mapped. Using Northern blotting analysis a striking difference in mRNA expression of Pmel17/gp100 and TYRP1/gp75 was found comparing skin samples of solid‐coloured (normal level) and grey horses (low level) as well as horse melanoma tumour samples (high). Staining of skin samples with antibodies recognizing the product of Pmel17/gp100, confirmed the results of the corresponding Northern blotting analysis. It seems that Pmel17/gp100 and TYRP1/gp75 are involved in progressive greying of horses. No mutation was found in a partial sequence of equine Cdkn2a/p16 analysed so far. Thus, the relation between equine melanoma susceptibility and Cdkn2a/p16 is subject to further investigation.