Genetic mapping of a Ptch1-associated rhabdomyosarcoma susceptibility locus on mouse chromosome 2
Genetic mapping of a Ptch1-associated rhabdomyosarcoma susceptibility locus on mouse chromosome 2
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DOI：
10.1016/j.ygeno.2004.07.002
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发表时间：
2004-11-01
期刊：
影响因子：
4.4
通讯作者：
Rosemann, M
中科院分区：
文献类型：
--
作者：
Hahn, H;Nitzki, F;Rosemann, M
补丁基因(PTCH I)的突变是导致各种家族性和散发性癌症的原因。缺失外显子6和7的PTCH(ne67/+)小鼠对类似于人横纹肌肉瘤(RMS)的肌肉肿瘤的发生表现出遗传背景依赖性的易感性，BALB/c(BALB)是敏感株，而C57BL/6(B6)则表现出抗性。利用B6x(BALB X 136)回交产生的Ptch小鼠进行全基因组连锁分析，以确定与RMS易感性相关的基因座，利用以肿瘤潜伏期为定量参数的数量性状基因座定位，在D2Mit37和D2Mit102(LRS=10)之间的2号染色体上检测到显著的RAMS易感基因座Parms1](Patted-Association RMS1)。Kaplan-Meier生存曲线显示，与B6等位基因纯合子小鼠相比，B6/BALB基因纯合子小鼠发生肿瘤的频率更高、速度更快(P=0.02)。还检测到了其他未达到连锁显着性的髓母细胞瘤耐药基因座。(C)2004 Elsevier Inc.保留所有权利。
Mutations in the Patched (Ptch I) gene are responsible for various familial and sporadic cancers. Ptch(neo67/+) mice, in which exons 6 and 7 are deleted, show genetic background-dependent susceptibility to the development of muscle tumors resembling human rhabdomyosarcoma (RMS), BALB/c (BALB) is a susceptible strain whereas C57BL/6 (B6) shows resistance. A genome-wide linkage analysis was carried out using Ptch mice produced from B6 x (BALB x 136) backcrosses to identify loci involved in the control of RMS susceptibility, Quantitative trait locus mapping with the censored tumor latency time as the quantitative parameter was used to detect a significant RAMS susceptibility modifier locus, Parms1] (Patched-Associated RMS 1), on chromosome 2 between D2Mit37 and D2Mit102 (LRS = 10). A Kaplan-Meier survival curve revealed that mice with the B6/BALB genotype develop tumors more frequently and much faster as compared to mice homozygous for the B6 allele (P = 0.02). Additional loci not reaching linkage significance were also detected for medulloblastoma resistance. (C) 2004 Elsevier Inc. All rights reserved.