2001 Fiscal Year Final Research Report Summary
Fine chromosomal localization and biological characterization of the mouse Par2 gene that confers resistance against urethane-induction of pulmonary adenomas.
| Project/Area Number |
12470059
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Japanese Foundation for Cancer Research |
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Principal Investigator |
KITAGAWA Tomoyuki Cancer Institute, Director, 癌研究所, 所長 (50085619)
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| Co-Investigator(Kenkyū-buntansha) |
LEE Gang-hong , 財団法人・冲中記念成人病研究所, 研究員 (10261405)
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| Project Period (FY) |
2000 – 2001
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| Keywords | mouse / lung tumor / resistance gene / chromosome / fine mapping / urethane |
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| Research Abstract |
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
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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
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Research Products
(2 results)
