Kazianis Steven, Khanolkar Vandeeta A, Nairn Rodney S, Rains J Douglas, Trono David, Garcia Rachel, Williams Earlanda L, Walter Ronald B
Molecular Biosciences Research Group, Texas State University, Dept of Chemistry and Biochemistry, San Marcos, TX, USA.
Comp Biochem Physiol C Toxicol Pharmacol. 2004 Jul;138(3):291-9. doi: 10.1016/j.cca.2004.08.003.
Xiphophorus fishes and their hybrids are used as models for the study of melanoma and other diseases. The cyclin-dependent kinase inhibitor gene family in humans is comprised of four members, including CDKN2A (P16), and dysregulation of this gene is implicated in numerous neoplasms including melanomas. We have investigated the status of the gene family in the southern platyfish X. maculatus. Xiphophorus harbors at least two such loci, which we now term CDKN2A/B and CDKN2D. Both loci map to Xiphophorus linkage group 5, a genomic area that has long been known to harbor the DIFF tumor suppressor locus. Within this report, we report on the complete cloning, genomic exon/intron boundary delineation, linkage mapping and expressional characteristics of Xiphophorus CDKN2D. We also compare and contrast this expression to that of the previously isolated CDKN2AB locus in normal and neoplastic tissues derived from non-hybrid and hybrid fishes. The hypothetical evolutionary relationships of gene family members and their involvement in melanoma is evaluated. In comparison to CDKN2A/B, the RNA expression of Xiphophorus CDKN2D differs in normal tissues and is not associated with melanotic/pathologic tissues, confirming functional divergence between obvious homologues.
剑尾鱼及其杂交种被用作研究黑色素瘤和其他疾病的模型。人类细胞周期蛋白依赖性激酶抑制剂基因家族由四个成员组成，包括CDKN2A（P16），该基因的失调与包括黑色素瘤在内的多种肿瘤有关。我们研究了南方剑尾鱼（X. maculatus）中该基因家族的状况。剑尾鱼至少有两个这样的基因座，我们现在将其命名为CDKN2A/B和CDKN2D。这两个基因座都定位于剑尾鱼连锁群5，这是一个长期以来已知含有DIFF肿瘤抑制基因座的基因组区域。在本报告中，我们报告了剑尾鱼CDKN2D的完整克隆、基因组外显子/内含子边界划定、连锁图谱绘制和表达特征。我们还比较了该基因在正常组织和肿瘤组织中的表达情况，这些组织来自非杂交和杂交鱼类，同时也与之前分离出的CDKN2AB基因座进行了对比。我们评估了基因家族成员的假设进化关系及其与黑色素瘤的关系。与CDKN2A/B相比，剑尾鱼CDKN2D的RNA表达在正常组织中有所不同，并且与黑色素沉着/病理组织无关，这证实了明显同源物之间的功能差异。
