IMMUNOLOGICAL ASPECTS OF AGING

这项建议的长期目标是研究 几种基因和环境因素对寿命和寿命的影响 证明这些基因之间的相互作用在 由于个体基因的存在而赋予更长的寿命。我们会 (A)利用同源基因研究一个基因区域(HB-2)在寿命中的作用 不同品系的老鼠。将使用三种毒株：B10(H-2b)；B10.D2/NSN (H-2d)和B10.BR(H-2k)及其杂交种的成活率较高 具有H-2杂合性。这项研究还将测试亚区是否 位于K端或D端附近的H-2很重要。对于…的效果 我们将比较(B10.A x B10.D2/NSN)F1的K端。我们会(二)研究 利用杂交和重组技术研究几个基因区域在生命周期中的作用 线条，尤指携带H-2的17号染色体的一段， 4号染色体携带B和性。这些细分市场将使用以下工具进行调查 回交小鼠(C57BL/6xDBA/2)F1×DBA/2、重组系及F2代 由交配(C57BL/6 x DBA/2)F1小鼠产生。利用回交小鼠，我们将 试图确认4号染色体携带b的片段的作用 在一生中与性互动，并发现杂合性越强， 寿命越长。此外，这些相互作用的作用和b 在免疫活力和非淋巴瘤实体瘤发展中的位置 被研究。一个或多个杂合性之间的遗传交互作用 第二个或多个基因座上的基因座和纯合性将影响寿命 使用F2d杂交小鼠进行了研究。例如，互动 在H-2b/H-2b、H-2b/H-2d、H-2d/H-2d之间 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 确定是否有其他遗传系统(纯合或杂合) 对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，重组系之间的 C57BL/6和DBA/2将比较来自于 这样的染色体会对寿命产生影响。我们的研究 将尝试将基因类型与与衰老相关的疾病模式联系起来 和免疫紊乱。免疫缺陷和与之相关的疾病 小鼠的一些基因类型可能有助于未来识别类似的 男人之间的关系。

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.