参与小鼠浆细胞瘤发生的肿瘤易感性基因的遗传定位。
Genetic mapping of tumor susceptibility genes involved in mouse plasmacytomagenesis.
作者信息
Mock B A, Krall M M, Dosik J K
机构信息
Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
出版信息
Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9499-503. doi: 10.1073/pnas.90.20.9499.
Plasmacytomas (PCTs) were induced in 47% of BALB/cAnPt mice by the intraperitoneal injection of pristane, in 2% of (BALB/c x DBA/2N)F1, and in 11% of 773 BALB/cAnPt x (BALB/cAnPt x DBA/2N)F1 N2 backcross mice. This result indicates a multigenic mode of inheritance for PCT susceptibility. To locate genes controlling this complex genetic trait, tumor susceptibility in backcross progeny generated from BALB/c and DBA/2N (resistant) mice was correlated with alleles of 83 marker loci. The genotypes of the PCT-susceptible progeny displayed an excess homozygosity for BALB/c alleles within a 32-centimorgan stretch of mouse chromosome 4 (> 95% probability of linkage) with minimal recombination (12%) near Gt10. Another susceptibility gene on mouse chromosome 1 may be linked to Fcgr2 (90% probability of linkage); there were excess heterozygotes for Fcgr2 among the susceptible progeny and excess homozygotes among the resistant progeny. Regions of mouse chromosomes 4 and 1 that are correlated with PCT susceptibility share extensive linkage homology with regions of human chromosome 1 that have been associated with cytogenetic abnormalities in multiple myeloma and lymphoid, breast, and endocrine tumors.
通过腹腔注射 pristane，47% 的 BALB/cAnPt 小鼠诱发了浆细胞瘤（PCTs），2% 的（BALB/c×DBA/2N）F1 小鼠以及 11% 的 773 只 BALB/cAnPt×（BALB/cAnPt×DBA/2N）F1 N2 回交小鼠诱发了浆细胞瘤。这一结果表明 PCT 易感性的多基因遗传模式。为了定位控制这种复杂遗传性状的基因，将 BALB/c 和 DBA/2N（抗性）小鼠产生的回交后代中的肿瘤易感性与 83 个标记位点的等位基因相关联。PCT 易感后代的基因型在小鼠 4 号染色体的 32 厘摩区域内显示出 BALB/c 等位基因的纯合性过高（连锁概率>95%），在 Gt10 附近的重组率极低（12%）。小鼠 1 号染色体上的另一个易感基因可能与 Fcgr2 连锁（连锁概率为 90%）；易感后代中 Fcgr2 的杂合子过多，抗性后代中纯合子过多。与 PCT 易感性相关的小鼠 4 号和 1 号染色体区域与人类 1 号染色体区域具有广泛的连锁同源性，人类 1 号染色体区域与多发性骨髓瘤以及淋巴、乳腺和内分泌肿瘤的细胞遗传学异常有关。
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