IMMUNOLOGICAL ASPECTS OF AGING

衰老的免疫学方面

• 批准号: 3114406
• 负责人: EDMOND J YUNIS
• 金额: $ 13.98万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-04-01 至 1990-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3114406
• 关键词: aging; alleles; antibody formation; autoimmune disorder; cellular immunity; fusion gene; gender difference; genetic recombination; genetic strain; genotype; haploidy; heterozygote; histocompatibility gene; humoral immunity; immunogenetics; immunoregulation; laboratory mouse; leukocyte antigen typing; longevity; longitudinal animal study

The long term objectives of this proposal are to study the interaction of the effect of several genes and environmental factors on life span and to demonstrate that the interactions between these genes are as important in conferring longer life span as the presence of individual genes. We will (a) study the role of one genetic region (Hb-2) in life span using congenic strains of mice. Three strains will be used: B10 (H-2b); B10.D2/nSn (H-2d) and B10.BR (H-2k) and hybrids among them to rank higher survival with heterozygosity of H-2. The study will also test whether subregions of H-2 located near the K end or the D end are important. For the effect of the K end we will compare (B10.A x B10.D2/nSn)F1. We will (b) study the role of several genetic regions in life span using hybrids and recombinant lines, especially a segment of Chromosome 17 carrying H-2, a segment of Chromosome 4 carrying b and sex. These segments will be investigated using backcross mice (C57BL/6xDBA/2)F1 x DBA/2, recombinant lines; and F2 hybrids produced by mating (C57BL/6 x DBA/2)F1 mice. Using backcross mice we will attempt to confirm the role of the segment of Chromosome 4 carrying b interacting with sex in life span and finding that the more heterozygosity, the longer the life span. Also, the role of these interactions and the b locus in immune vigor and in development of non-lymphoma solid tumors will be studied. The genetic interaction between heterozygosity at one or more loci and homozygosity at a second or more loci affecting life span will be investigated using the F2d hybrid mice. For example, the interaction between H-2b/H-2b, H-2b/H-2d, H-2d/H-2d will be studied with respect to MUP-1a/MUP-1a, MUP-1a/MUP-1b and MUP-1b/MUP-1b and sex because the MUP-1 is a genetic marker of the segment of Chromosome 4 carrying b. We will also determine if other genetic systems (homozygous or heterozygous) in addition to H-2, MUP-1 or sex influence life span (Idh-1, Gpd-1, Gpi-1, Hbb,Mod-1, esterase D and C8). On the other hand, the recombinant lines between C57BL/6 and DBA/2 will compare the number of dominant alleles derived from such chromosomes which will produce an effect on life span. Our studies will attempt to relate genotypes to disease patterns associated with aging and immune disturbances. Immune deficiencies and diseases associated with some genotypes in mice may help future attempts to identify similar relationships in man.

该提案的长期目标是研究以下因素之间的相互作用： 多种基因和环境因素对寿命的影响 证明这些基因之间的相互作用同样重要 由于个体基因的存在而赋予更长的寿命。 我们将 (a) 使用同源基因研究一个遗传区域 (Hb-2) 在寿命中的作用 小鼠品系。 将使用三种菌株：B10 (H-2b)； B10.D2/nSn (H-2d) 和 B10.BR (H-2k) 以及它们之间的杂种，生存率更高 具有H-2杂合性。 该研究还将测试各次区域是否 位于K端或D端附近的H-2很重要。 为了达到这样的效果 K 端我们将比较 (B10.A x B10.D2/nSn)F1。 我们将 (b) 研究 使用杂交和重组技术研究几个遗传区域在生命周期中的作用 线，尤其是携带 H-2 的 17 号染色体的一段， 4 号染色体携带 b 和性别。 这些细分市场将使用以下方式进行调查 回交小鼠 (C57BL/6xDBA/2)F1 x DBA/2，重组系；和F2杂交种 由 (C57BL/6 x DBA/2)F1 小鼠交配产生。 使用回交小鼠，我们将 尝试确认携带 b 的 4 号染色体片段的作用 在生命周期中与性相互作用并发现杂合性越多， 寿命越长。 此外，这些相互作用的作用和b 免疫活力和非淋巴瘤实体瘤发展中的位点将 被研究。 一个或多个杂合性之间的遗传相互作用 影响寿命的第二个或更多基因座的基因座和纯合性将 使用 F2d 杂交小鼠进行研究。 例如，交互 H-2b/H-2b、H-2b/H-2d、H-2d/H-2d 之间的研究将涉及 MUP-1a/MUP-1a、MUP-1a/MUP-1b 和 MUP-1b/MUP-1b 与性别，因为 MUP-1 是 携带b的4号染色体片段的遗传标记。 我们还将 确定是否还有其他遗传系统（纯合或杂合） H-2、MUP-1 或性别影响寿命（Idh-1、Gpd-1、Gpi-1、Hbb、Mod-1、 酯酶 D 和 C8)。 另一方面，重组系 C57BL/6 和 DBA/2 将比较源自的显性等位基因的数量 这样的染色体会对寿命产生影响。 我们的研究 将尝试将基因型与与衰老相关的疾病模式联系起来 和免疫紊乱。 免疫缺陷和相关疾病 小鼠的一些基因型可能有助于未来识别类似的基因型 人身上的关系。