Application of Genetics and Physiological Genomics to Dissect Resistance to T1D
应用遗传学和生理基因组学剖析 T1D 抗性
基本信息
- 批准号:6990084
- 负责人:
- 金额:$ 15.65万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2005
- 资助国家:美国
- 起止时间:2005-07-01 至 2010-01-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Type 1 diabetes (T1D) is one of the prototypical organ-specific autoimmune endocrinopathies that results in life-long dependency on daily insulin injection. Molecular genetic approaches have identified regions of the human, mouse, rat genomes that play a role in susceptibility to Type 1 Diabetes (T1D). While the major histocompatibility complex (MHC), the equivalent of the human leukocyte antigen (HLA), is the major locus responsible for susceptibility to T1D, there is a separate set of genes that contribute to susceptibility and end organ damage. We have been studying the genetic factors contributing to T1D in the BBDP rat, a model of spontaneous disease concurrent with lymphopenia. We have identified the location of five loci involved in
T1D: Iddm2/lyp, lddm1/MHC, Iddm3, Iddm19, and a fifth locus on chromosome 4 (Iddm4?). Given the identification of the Ian5 mutation as the gene responsible for Iddm2/lyp, we now focus on the identification of the additional factors playing a role in T1D in the BB rat. Our mapping studies have identified four diabetogenic loci in addition to the MHC, which Projects 3 specifically addresses, in close collaboration with Project 1. The focus of Project 3 is to generate consomic and derived congenic strains for three additional factors, including Iddm3, Iddm19, and the susceptibility locus on chromosome 4 nearby Ian5 (Project 1) and to evaluate these new models for their role in T1D using gene expression profiling, comparative genomics, and sequence analysis. Furthermore, we are developing the technology to knock genes out in the rat for
validation of positionally cloned genes. Specifically we will: 1. Continue positional cloning efforts for Iddm3 to identify sequence variants contributing to resistance to autoimmune diabetes.
2. Follow up a second resistance factor on chromosome 15. 3. Use novel 70-mer oligonucleotide and cDNA microarray platforms to evaluate genes and pathways affected by the diabetogenic factors identified in the BB rat. 4. Generate rat ENU-induced knockout strains to validate genes involved in autoimmune diabetes in the BB rat.
1型糖尿病(T1 D)是一种典型的器官特异性自身免疫性内分泌疾病,导致终身依赖每日胰岛素注射。分子遗传学方法已经确定了人类,小鼠,大鼠基因组中在1型糖尿病(T1 D)易感性中发挥作用的区域。虽然主要组织相容性复合体(MHC),相当于人类白细胞抗原(HLA),是负责T1 D易感性的主要位点,但还有一组单独的基因导致易感性和终末器官损伤。我们一直在研究BBDP大鼠(一种自发性疾病伴淋巴细胞减少症的模型)中导致T1 D的遗传因素。我们已经确定了五个基因座的位置,
T1 D:Iddm 2/lyp、lddm 1/MHC、Iddm 3、Iddm 19和4号染色体上的第5个位点(Iddm 4?)。鉴于Ian 5突变作为Iddm 2/lyp基因的鉴定,我们现在专注于鉴定在BB大鼠T1 D中发挥作用的其他因素。除了项目3专门针对的MHC之外,我们的绘图研究还与项目1密切合作,确定了四个致糖尿病基因座。项目3的重点是产生三个额外的因素,包括Iddm 3,Iddm 19,和4号染色体上的易感基因位点附近的Ian 5(项目1),并评估这些新的模型在T1 D中的作用,使用基因表达谱,比较基因组学和序列分析。此外,我们正在开发一种技术,可以敲除老鼠的基因,
定位克隆基因的验证。具体来说,我们将:1。继续Iddm 3的定位克隆工作,以鉴定有助于抵抗自身免疫性糖尿病的序列变体。
2.追踪15号染色体上的第二个抵抗因子。3.使用新的70聚体寡核苷酸和cDNA微阵列平台,以评估基因和途径影响的糖尿病因素中确定的BB大鼠。4.产生大鼠ENU诱导的敲除菌株,以验证BB大鼠中涉及自身免疫性糖尿病的基因。
项目成果
期刊论文数量(0)
专著数量(0)
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会议论文数量(0)
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ANNE E. KWITEK其他文献
ANNE E. KWITEK的其他文献
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{{ truncateString('ANNE E. KWITEK', 18)}}的其他基金
Identification of a metabolic syndrome transcriptome signature in the LH rat
LH 大鼠代谢综合征转录组特征的鉴定
- 批准号:
8098029 - 财政年份:2010
- 资助金额:
$ 15.65万 - 项目类别:
Identification of a metabolic syndrome transcriptome signature in the LH rat
LH 大鼠代谢综合征转录组特征的鉴定
- 批准号:
7963802 - 财政年份:2010
- 资助金额:
$ 15.65万 - 项目类别:
Dissecting the genetics of the Metabolic Syndrome on Chromosome 17 of the LH rat
剖析 LH 大鼠 17 号染色体代谢综合征的遗传学
- 批准号:
7624320 - 财政年份:2008
- 资助金额:
$ 15.65万 - 项目类别:
Dissecting the genetics of the Metabolic Syndrome on Chromosome 17 of the LH rat
剖析 LH 大鼠 17 号染色体代谢综合征的遗传学
- 批准号:
7460150 - 财政年份:2008
- 资助金额:
$ 15.65万 - 项目类别:
Dissecting the genetics of the Metabolic Syndrome on Chromosome 17 of the LH rat
剖析 LH 大鼠 17 号染色体代谢综合征的遗传学
- 批准号:
7825390 - 财政年份:2008
- 资助金额:
$ 15.65万 - 项目类别:
Dissecting the genetics of the Metabolic Syndrome on Chromosome 17 of the LH rat
剖析 LH 大鼠 17 号染色体代谢综合征的遗传学
- 批准号:
8066351 - 财政年份:2008
- 资助金额:
$ 15.65万 - 项目类别:
Dissecting the genetics of the Metabolic Syndrome on Chromosome 17 of the LH rat
剖析 LH 大鼠 17 号染色体代谢综合征的遗传学
- 批准号:
8411732 - 财政年份:2008
- 资助金额:
$ 15.65万 - 项目类别: