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Fine chromosomal localization and biological characterization of the mouse Par2 gene that confers resistance against urethane-induction of pulmonary adenomas.

小鼠 Par2 基因的精细染色体定位和生物学特征，赋予其对氨基甲酸酯诱导的肺腺瘤的抵抗力。

基本信息

批准号：
12470059
负责人：
KITAGAWA Tomoyuki
金额：
$ 6.72万
依托单位：
Japanese Foundation for Cancer Research
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470059/
关键词：
mouse lung tumor resistance gene chromosome fine mapping urethane candidate positional cloning

项目摘要

BALB/cByJ mice are 14 times more resistant to urethane-induction of pulmonary adenomas than the susceptible A/J strain. Our previous linkage analysis of (A/J x BALB/cByJ)F_1 x AIJ backcross mice provided statistical evidence that a major resistance locus of BALB/cByJ with a dominant effect, designated Par2 (Pulmonary adenoma resistance 2), exists within an approximately 25 cM section of distal chromosome 18. To facilitate molecular identification of the Par2 locus, the present study was conducted to finely localize its chromosomal position utilizing Par2-congenic mice. Male BALB/cByJ mice were mated with female C57BL/6J mice carrying recessive Par2 alleles and their male F_1 progeny were backcrossed to female BALB/cByJ mice. A male backcross mouse heterozygous within the Par2 interval of 25 cM was randomly selected and again backcrossed to female BALB/cByJ mice. This backcross-selection cycle was simply repeated to produce semi-congenic mice with a general BALB/cByJ genetic background … More except for the Par2 interval, where the mice were heterozygous with paternal C57BL/6J alleles and maternal BALB/cByJ alleles. After the 6th or 7th backcross, 9 male mice possessing a recombination within the paternal Par2 interval were retained and crossed to female A/J mice. Resultant progeny were treated with urethane and examined for lung tumor development in order to deduce the Par2 genotypes of the recombinants through linkage analysis. By comparing the deduced Par2 genotype of each recombinant with its recombinational breakpoint, the Par2 locus was confined to an approximately 0.5 cM region flanked by D18Mit103 and D18Mit188 loci. Our results indicate that fully congenic mice conventionally established by at least 9 simple backcrosses or by the speed congenic method are not necessarily required for fine mapping of quantitative trait loci. In the case of the Par2 locus, we found that semi-congenic mice after as few as 4 simple backcrosses were useful for this purpose. The map information obtained in this study should enable subsequent positional cloning of the Par2 gene. Less

BALB/cByJ小鼠对肺腺瘤的耐受性比敏感的A/J品系高14倍。我们先前对（A/J × BALB/cByJ）F_1 × AIJ回交小鼠的连锁分析提供了统计学证据，即BALB/cByJ的一个具有显性效应的主要抗性位点，命名为Par 2（肺腺瘤抗性2），存在于18号染色体远端约25 cM的区段内。为了便于分子鉴定的Par 2基因座，本研究进行精细定位其染色体位置利用Par 2同源小鼠。雄性BALB/cByJ小鼠与携带隐性Par 2等位基因的雌性C57 BL/6 J小鼠交配，其F_1代雄性与雌性BALB/cByJ小鼠回交。随机选择在25 cM的Par 2间隔内杂合的雄性回交小鼠，并再次与雌性BALB/cByJ小鼠回交。简单地重复该回交选择循环以产生具有一般BALB/cByJ遗传背景的半同源小鼠 ...更多信息除了Par 2间隔，其中小鼠是杂合的，具有父本C57 BL/6 J等位基因和母本BALB/cByJ等位基因。在第6次或第7次回交后，保留9只在父本Par 2间隔内具有重组的雄性小鼠，并与雌性A/J小鼠杂交。用氨基甲酸乙酯处理所得后代，并检查肺肿瘤的发展，以通过连锁分析推断重组体的Par 2基因型。通过比较每个重组体的推导的Par 2基因型与其重组断点，Par 2基因座被限制在侧接D18 Mit 103和D18 Mit 188基因座的约0.5cM区域。我们的研究结果表明，完全同源小鼠通常建立了至少9个简单的回交或速度同源的方法不一定需要精细的数量性状基因座的定位。在Par 2基因座的情况下，我们发现，在少至4个简单的回交后的半同源小鼠可用于此目的。在这项研究中获得的地图信息，使随后的定位克隆Par 2基因。少