Nairn R S, Coletta L D, McEntire B B, Walter R B, Morizot D C
Science Park-Research Division, University of Texas M.D. Anderson Cancer Center, Smithville 78957, USA.
Cancer Genet Cytogenet. 1996 Jun;88(2):144-50. doi: 10.1016/0165-4608(95)00296-0.
Using a p53 encoding cDNA fragment of rainbow trout (Oncorhynchus mykiss) as probe, a lambda clone from a platyfish (Xiphophorus maculatus) genomic library was isolated. DNA sequencing of the insert from this clone revealed that it contained the highly conserved domains IV and V of the p53 polypeptide. To map the Xiphophorus p53 gene, joint segregation analysis of the inheritance of a PstI-generated DNA restriction fragment length polymorphism (RFLP) and the inheritance of 36 polymorphic protein and DNA markers was performed in backcross hybrids of X. clemenciae x (X. clemenciae x X. milleri) and X. helleri x X. (helleri x X. maculatus Jp 163 B) using Oncorhynchus cDNA and Xiphophorus genomic p53 probes, respectively. The p53-hybridizing sequence (TP53) was linked to the ACO1 (cytosolic aconitase) locus in both crosses, and defines a new Xiphophorus linkage group, designated LG XIV. This is the first mapping assignment of a known human tumor suppressor gene in fish. Since ACO1 is not linked with melanoma severity in X. helleri x X. maculatus Jp 163 A backcross hybrids, these data indicate that homozygosity for the X. helleri TP53 genotype in backcross hybrids of the cross type is not associated with genetically regulated malignant melanoma formation in the Gordon-Kosswig hybrid melanoma model.
以虹鳟(Oncorhynchus mykiss)的p53编码cDNA片段为探针,从剑尾鱼(Xiphophorus maculatus)基因组文库中分离出一个λ克隆。对该克隆插入片段的DNA测序显示,它包含p53多肽的高度保守结构域IV和V。为了定位剑尾鱼的p53基因,分别使用虹鳟cDNA和剑尾鱼基因组p53探针,在X. clemenciae x(X. clemenciae x X. milleri)和X. helleri x X.(helleri x X. maculatus Jp 163 B)的回交杂种中,对PstI产生的DNA限制性片段长度多态性(RFLP)的遗传以及36个多态性蛋白质和DNA标记的遗传进行了联合分离分析。在这两个杂交组合中,p53杂交序列(TP53)都与ACO1(胞质乌头酸酶)基因座连锁,并定义了一个新的剑尾鱼连锁群,命名为LG XIV。这是鱼类中已知人类肿瘤抑制基因的首次定位。由于在X. helleri x X. maculatus Jp 163 A回交杂种中ACO1与黑色素瘤严重程度不连锁,这些数据表明在该杂交类型的回交杂种中,X. helleri TP53基因型的纯合性与戈登 - 科斯维格杂种黑色素瘤模型中基因调控的恶性黑色素瘤形成无关。