THE MOUSE FAS-LIGAND GENE IS MUTATED IN GLD MICE AND IS PART OF A TNF FAMILY GENE-CLUSTER
THE MOUSE FAS-LIGAND GENE IS MUTATED IN GLD MICE AND IS PART OF A TNF FAMILY GENE-CLUSTER
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DOI：
10.1016/1074-7613(94)90106-6
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发表时间：
1994-05-01
期刊：
影响因子：
32.4
通讯作者：
SELDIN, MF
中科院分区：
文献类型：
--
作者：
LYNCH, DH;WATSON, ML;SELDIN, MF
克隆小鼠Fas配体的基因并确定其染色体位置。FasL与小鼠1号染色体上的gld紧密连锁（在567次减数分裂事件中没有交叉），并与同一TNF家族的配体Ox40配体（Ox40l，在567次减数分裂事件中有1次交叉）的新成员紧密连锁。Southern印迹分析未发现gld和野生型小鼠的FasL基因之间存在任何差异，并且在PMA和离子霉素诱导的野生型和共基因gld T细胞中FasL mRNA转录物的水平相似。gld基因的序列分析表明，一个单一的氨基酸变化（苯丙氨酸亮氨酸）在COOH末端部分的这种II型跨膜蛋白，COS细胞转染FasL的cDNA从gld小鼠未能诱导细胞凋亡的pas表达的靶细胞。因此，数据表明，gld表型是FasL基因中的点突变的结果，并且FasL是与小鼠1号染色体的小区域内的TNF定位结构相关的配体复合物的一部分。
The gene for the mouse Fas ligand was cloned and its chromosomal position determined. Fasl was tightly linked to gld (no crossovers in 567 meiotic events) on mouse chromosome 1 and closely linked with a novel member of the same TNF family of ligands, the Ox40 ligand (Ox40l, 1 crossover in 567 meiotic events). Southern blot analysis did not reveal any difference between the Fasl gene from gld and wild-type mice and levels of Fasl mRNA transcripts were similar in PMA and ionomycin induced wild-type and coisogenic gld T cells. Sequence analysis of the gld gene indicated a single amino acid change(Phe Leu) in the COOH terminal portion of this type II transmembrane protein, and COS cells transfected with Fasl cDNA from gld mice failed to induce apoptosis of pas-expressing target cells. Thus, the data demonstrate that the gld phenotype is the result of a point mutation in the Fasl gene and that Fasl is part of a complex of ligands structurally related to TNF mapping within a small region of mouse chromosome 1.