Studies on background genes aggravating lpr^<cg>-induced nephritis and complementation between lpr^<cg> and gld genes

lpr^<cg>肾炎加重背景基因及lpr^<cg>与gld基因互补研究

• 批准号: 04454185
• 负责人: MATSUZAWA Akio
• 金额: $ 4.22万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04454185/
• 关键词: Lpr^<cg> gene; Gld gene; Autoimmunity; MRL mice; Nephritis; Complementation; Lymphadenopathy; Homing; 自己免疫病; 全身性リンパ節腫脹

Linkage tests were conducted using the intersubspecific backcross of (CBA-lpr^<cg> x MOL-MIT)F_1 x CBA-lpr^<cg> and led to the conclusion that the lpr^<cg> gene locates between Ly-44 and Tdt on chromosome 19 at the distances : centromere-Ly-44 -(17.0 cM)-lpr^<cg>-(5.3 cM)-Tdt-telomere.Both homozygous and heterozygous lpr^<cg> gene induced more severe autoimmune syndromes, nephritis and vasculitis on the MRL than the CBA background. To analyze the effects of background genes, backcross offspring were examined from the interspecific cross of (MRL-lpr x CAST/Ei)F_1 x MRL-lpr. The profound effects of background genes on the extent of nephritis, lymphadenopathy and anti-DNA antibody were demonstrated. Of major note, this study suggested the identification of chromosomal positions for genes that modify nephritis. Analysis of the backcross mice for markers covering most of the mouse genome suggest that over 50% of the variance in renal disease is attributable to quantitative trait loci on mouse chromosomes 7 and 12. These loci may also participate in aggravation of lpr^<cg>-induced nephritis.Simultaneous bone marrow (BM) and lymph node (LN) transplantation into (CBA x C3H)F_1 (F_1) mice was performed in various genotype combinations. Grafted C3H-lpr/lpr and CBA-lpr^<cg> LN swelled but +/+ and C3H-gld/gld LN strophied in recipients of lpr/lpr or lpr^<cg>/lpr^<cg> BM.All LN of these genotypes swelled in recipients of gld/gld BM.Thus, lpr and lpr^<cg> are phenotypically different from gld in the interaction of BM-derived double negative (DN) T cells and +/+ LN.Lymphadenopathy induced by the cooperation between lpr^<cg> and gld was confirmed to be lpr but not of gld phenotype by a similar method.

利用（CBA-lpr^ x MOL-MIT）F_1 x CBA-lpr^的亚种间回交进行连锁分析<cg><cg>，结果表明lpr^<cg>基因位于19号染色体Ly-44和Tdt之间，其距离为：着丝粒-Ly-44 -（17.0 cM）-lpr^<cg>-（5.3 cM）-Tdt-端粒，纯合和杂合的lpr^<cg>基因在MRL上均比CBA背景下诱发更严重的自身免疫综合征、肾炎和血管炎。为了分析背景基因的作用，对（MRL lpr × CAST/Ei）F_1 × MRL lpr的回交后代进行了检测。背景基因对肾炎、淋巴结病和抗DNA抗体的程度有深刻的影响。值得注意的是，这项研究提出了修改肾炎基因的染色体位置的鉴定。对回交小鼠进行的覆盖大部分小鼠基因组的标记分析表明，肾脏疾病中超过50%的变异可归因于小鼠7号和12号染色体上的数量性状基因座。本研究<cg>采用骨髓（BM）和淋巴结（LN）同时移植的方法，将不同基因型组合的骨髓移植到（CBA × C3 H）F_1（F_1）小鼠体内。在lpr/lpr和lpr^ /lpr^ BM受体中，移植的C3 H-lpr/lpr和CBA-lpr ^<cg>LN肿胀，而+/+和C3 H-gld/gld LN肿胀<cg><cg>，在gld/gld BM受体中，这些基因型的LN均肿胀。因此，<cg>在BM源性双阴性（DN）T细胞与+/+ LN的相互作用中，lpr和lpr^与gld的表型不同<cg>。

项目成果

Watanabe, T., Sakai, Y., Hanai, A., Masaki, S., Ohno, . K., Miyawaki, S.and Matsuzawa, A.: "A new allele at the lpr gene on chromosome 19 expresses properties different from the original recessive mutation." Mammaliam Genome. 4. 346-347 (1993)

渡边，T.，酒井，Y.，花井，A.，正树，S.，大野，。

Akio Matsuzawa: "A crucial role of the thymus in induction by lpr^<cg> gene of lymphadenopathy with autoimmunity in the mouse" Immunology. 75. 688-692 (1992)

Akio Matsuzawa：“胸腺在 lpr^<cg> 基因诱导小鼠自身免疫性淋巴结病中的关键作用”免疫学。

Motomu Shimizu: "Cell electrophoretic characterization of abnormally expanded lymphocytes in autoimmune lpr^<cg>,lpr,gld and Yaa mice and thymocyte subsets" Journal of Electrophoresis. 13. 136-142 (1992)

Motomu Shimizu：“自身免疫性 lpr^<cg>、lpr、gld 和 Yaa 小鼠和胸腺细胞亚群中异常增殖的淋巴细胞的细胞电泳特征”《电泳杂志》。

Matsuzawa, A., Katagiri, T., Ogata, Y., Kominami, R.and Kimura, M.: "Lymphadenopathy induced by the cooperation between lpr^<cg> and gld genes is of lpr but not of gld phenotype." European Journal of Immunology. (in press). (1994)

Matsuzawa, A.、Katagiri, T.、Ogata, Y.、Kominami, R.和 Kimura, M.：“lpr^<cg> 和 gld 基因之间的合作诱导的淋巴结病是 lpr 但不是 gld 表型。”

Mikio Kimura: "Nephritogenicity of lpr^<cg> gene on the MRL background" Immunology. 76. 498-504 (1992)

Mikio Kimura：“MRL 背景下 lpr^<cg> 基因的肾致原性”免疫学。