Lynch D H, Watson M L, Alderson M R, Baum P R, Miller R E, Tough T, Gibson M, Davis-Smith T, Smith C A, Hunter K
Department of Immunobiology, Immunex Research and Development Corporation, Seattle, Washington 98101.
Immunity. 1994 May;1(2):131-6. doi: 10.1016/1074-7613(94)90106-6.
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 Fas-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.
克隆了小鼠Fas配体的基因并确定了其染色体位置。Fasl与小鼠1号染色体上的gld紧密连锁（在567次减数分裂事件中无交叉），并与同一TNF配体家族的一个新成员Ox40配体（Ox40l，在567次减数分裂事件中有1次交叉）紧密连锁。Southern印迹分析未揭示gld小鼠和野生型小鼠的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同基因gld T细胞中，Fasl mRNA转录本水平相似。gld基因的序列分析表明，在这种II型跨膜蛋白的COOH末端部分存在单个氨基酸变化（苯丙氨酸→亮氨酸），并且用gld小鼠的Fasl cDNA转染的COS细胞未能诱导表达Fas的靶细胞凋亡。因此，数据表明gld表型是Fasl基因中一个点突变的结果，并且Fasl是与位于小鼠1号染色体小区域内的TNF结构相关的配体复合物的一部分。
