CONGENIC STRAINS FOR GENES AFFECTING COLON TUMORS

影响结肠肿瘤的基因同源菌株

• 批准号: 2008395
• 负责人: ROSEMARY W ELLIOTT
• 金额: $ 18.34万
• 依托单位: ROSWELL PARK CANCER INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-30 至 1998-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2008395
• 关键词: alleles; animal breeding; cancer risk; chemical carcinogen; chemical carcinogenesis; chemical hypersensitivity; chemical related neoplasm /cancer; colon neoplasms; gel electrophoresis; gene expression; gene interaction; genetic strain; inbreeding; laboratory mouse; loss of heterozygosity; methylhydrazines; neoplasm /cancer genetics; northern blottings; phenotype; polymerase chain reaction; tumor promoters; western blottings

The overall goal of this proposal is to test which regions of the mouse genome, identified in preliminary experiments, have an effect on the number of colon tumors induced by a standard treatment with 1,2- dimethylhydrazine dihydrochloride (DMH). In an early study on sensitivity to DMH-induced colon tumors (Evans et al. 1977), the most sensitive strain was ICR/Ha (I), with 60/60 animals having large numbers of tumors after DMH treatment, while the most resistant strain was C57BL/6Ha (B), with 0/90 having tumors. All 68 1XB Fl hybrid animals developed tumors. In a backcross, (IXB)XB, 46/117 animals developed tumors. The IBB backcross has been repeated and tumors were detected in 40 of 122 progeny. SSR-PCR using primer pairs (Dietrich et al. 1992) has detected variation between strains 1 and B for 41% of the primer pairs tested. The 122 progeny have been typed for 90 loci with at least two loci per autosome. The data suggest that tumor formation is controlled by several genetic loci. The major locus, Ccs-1, on central Chr 12 was linked to Dl2Mit6 (p <0.001). Other genetic tests identified loci on Chrs 2, 3, 5,7, 9, 10, 14, 15 and 16. To determine whether or not the loci at the eleven genetic regions identified in the backcross affect DMH-induced tumor formation in mice, it is proposed to generate congenic strains in which, for each suspected locus, the allele from the sensitive strain is placed on the background of the resistant strain. The reciprocal congenic, in which the allele from the resistant strain is placed on the background of the sensitive strain, will -also be made. A total of 22 congenic strains are proposed. Animals from each of these congenic strains will be treated with DMH and the effect of each allele, in both the homozygous and heterozygous state, on tumor - susceptibility will be determined. Double congenic strains will be made and used to determine how pairs of loci interact. In the course of this work, the number of backcross progeny will be increased, which will improve the statistics of linkage and increase the number of tumor-bearing animals. Tumor DNA from different congenic strains will be used to test for loss of heterozygosity of candidate genes. Tumor RNA will be used to determine expression of candidate genes. DNA from existing inbred strains and existing congenic strains will be typed for loci used to obtain the framework map, especially those loci in the eleven identified regions, to identify strains differing at only l or 2 of these loci. Animals from these strains will be treated with DMH to determine the effects of alleles from these regions.

这个提议的总体目标是测试老鼠的哪些区域

项目成果

An interstitial telomere array proximal to the distal telomere of mouse chromosome 13.

靠近小鼠 13 号染色体远端端粒的间质端粒阵列。

• DOI: 10.1007/s003359900458
• 发表时间: 1997
• 期刊: Mammalian genome : official journal of the International Mammalian Genome Society
• 作者: Yen,CH;Pazik,J;Zhang,Y;Elliott,RW
• 通讯作者: Elliott,RW

Characterization of a Mus spretus YAC that maps to the pseudoautosomal region.

映射到假常染色体区域的 Mus spretus YAC 的表征。

• DOI: 10.1006/geno.1996.4462
• 发表时间: 1997
• 期刊: Genomics.
• 作者: Yen,CH;Elliott,RW
• 通讯作者: Elliott,RW

Human, viral or mutant human IL-10 expressed after local adenovirus-mediated gene transfer are equally effective in ameliorating disease pathology in a rabbit knee model of antigen-induced arthritis.

• DOI: 10.1186/ar1960
• 发表时间: 2006
• 期刊: Arthritis research & therapy
• 影响因子: 4.9
• 作者: Keravala A;Lechman ER;Nash J;Mi Z;Robbins PD
• 通讯作者: Robbins PD

Adverse effects of adenovirus-mediated gene transfer of human transforming growth factor beta 1 into rabbit knees.

• DOI: 10.1186/ar745
• 发表时间: 2003
• 期刊: Arthritis research & therapy
• 影响因子: 4.9
• 作者: Mi Z;Ghivizzani SC;Lechman E;Glorioso JC;Evans CH;Robbins PD
• 通讯作者: Robbins PD

A polymorphic interstitial telomere array near the center of mouse chromosome 8.

小鼠 8 号染色体中心附近的多态性间质端粒阵列。

• DOI: 10.1007/s003359900059
• 发表时间: 1996
• 期刊: Mammalian genome : official journal of the International Mammalian Genome Society
• 作者: Yen,CH;Pazik,J;Elliott,RW
• 通讯作者: Elliott,RW