Pataer A, Nishimura M, Kamoto T, Ichioka K, Sato M, Hiai H
Department of Pathology and Biology of Diseases, Kyoto University Graduate School of Medicine, Sakyo-ku, Japan.
Cancer Res. 1997 Jul 15;57(14):2904-8.
Development of pulmonary adenomas (PAs) in mice is under the genetic control of multiple host genes. We have established a new set of SMXA recombinant inbred strains from PA-susceptible A/J and PA-resistant SM/J mice. The number of urethan-induced PAs was variable among substrains of the SMXA recombinant inbred strains, indicating the involvement of multiple genes. SMXA24 mice were highly resistant to PA, although they had susceptible alleles at all four known susceptibility genes, including kras2 and MHC. To identify the resistance gene in SMXA24, progeny of reciprocal F1 crosses and progeny of backcrosses to A/J were given urethan at 4 weeks of age and examined for induced PA at the age of 5 months. In reciprocal F1 cross progeny, the incidence of PA was very low, indicating that the resistance was a semidominant trait. Quantitative trait analysis of the backcross generation revealed significant linkages to loci on chromosome 12 (logarithm of odds score, 6.47) and chromosome 11 (logarithm of odds score, 4.35). To date, two PA resistance (PAR) genes, Par1 (located on chromosome 11) and Par2 (located on chromosome 18), have been reported. From the map position, one of the resistance genes on chromosome 11 was indistinguishable from Par1. However, another resistance gene on chromosome 12 was new, and we named this gene Par3. A likely candidate gene for Par3 is nPKCn, which is expressed exclusively in skin and lung and is down-regulated in PA. Par1 and Par3 seemed to act synergistically.
小鼠肺腺瘤（PA）的发生受多个宿主基因的遗传控制。我们从PA易感的A/J小鼠和PA抗性的SM/J小鼠中建立了一组新的SMXA重组近交系。在SMXA重组近交系的亚系中，尿烷诱导的PA数量各不相同，这表明多个基因参与其中。SMXA24小鼠对PA具有高度抗性，尽管它们在所有四个已知的易感基因（包括kras2和MHC）上都有易感等位基因。为了鉴定SMXA24中的抗性基因，对正反交F1代的后代以及与A/J回交的后代在4周龄时给予尿烷，并在5月龄时检查诱导的PA。在正反交F1代杂交后代中，PA的发生率非常低，这表明抗性是一种半显性性状。对回交一代的数量性状分析显示与12号染色体上的位点（优势对数得分，6.47）和11号染色体上的位点（优势对数得分，4.35）有显著连锁。迄今为止，已经报道了两个PA抗性（PAR）基因，Par1（位于11号染色体上）和Par2（位于18号染色体上）。从图谱位置来看，11号染色体上的一个抗性基因与Par1无法区分。然而，12号染色体上的另一个抗性基因是新的，我们将这个基因命名为Par3。Par3的一个可能候选基因是nPKCn，它仅在皮肤和肺中表达，并且在PA中表达下调。Par1和Par3似乎协同发挥作用。
