A comparative genetic approach for the investigation of ageing grey horse melanoma
A comparative genetic approach for the investigation of ageing grey horse melanoma
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DOI：
10.1111/j.1439-0388.2000x.00245.x
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发表时间：
2000-04-01
期刊：
影响因子：
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通讯作者：
Stranzinger, G
中科院分区：
文献类型：
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作者：
Rieder, S;Stricker, C;Stranzinger, G
老年灰马特别容易患黑色素瘤。使用分离分析，对两个灰马家族群体 (n = 71) 的六种遗传和非通用（环境）模型进行了比较。多基因模型仍然比环境模型更好地拟合数据，表明遗传对该现象有很强的影响。对黑素细胞特异的两个基因 Pmel17/gp100 和 TYRP1/gp75 以及编码细胞周期调节剂抑制剂的基因 Cdkn2a/p16 进行了部分克隆、测序和作图。使用 Northern blotting 分析，比较纯色马（正常水平）和灰马（低水平）以及马黑色素瘤肿瘤样本（大腿）的皮肤样本，发现 Pmel17/gp100 和 TYRP1/gp75 的 mRNA 表达存在显着差异。用识别 Pmel17/gp100 产物的抗体对皮肤样本进行染色，证实了相应 Northern 印迹分析的结果。 Pmel17/gp100 和 TYRP1/gp75 似乎与马的渐进变白有关。迄今为止分析的马Cdkn2a/p16的部分序列未发现突变。因此，马黑色素瘤易感性与Cdkn2a/p16之间的关系有待进一步研究。
Ageing grey horses are particularly susceptible to melanoma. Using segregation 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 strong genetic impact on the phenomenon. Pmel17/gp100 and TYRP1/gp75, two genes which are specific for melanocytes, and Cdkn2a/p16 a gene coding tor 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 thigh). 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.