Protein trafficking during placental development: the role of TMED2

为了发现胚胎发育所需的基因，我们使用正向遗传筛选来鉴定E9.5异常和出生前死亡的小鼠突变体。在这个n -乙基-亚氮-尿素（ENU）隐性筛选中鉴定出99J系，因此该系中突变的基因是正常发育所必需的。99J纯合突变体胚胎早在E8.5发育迟缓，在E12.5死亡。在E9.5时，这些突变体的绒毛膜尿囊附着和迷宫发育失败。我们将99J突变定位到小鼠5F染色体上，发现了一个单点突变，点突变位于跨膜emp24结构域转运蛋白2 （p24beta/Tmed2，简称Tmed2）的第一个外显子上。该突变导致TMED2信号序列中的丙氨酸非同义替换为谷氨酸。我们还发现该突变导致99J纯合突变胚中TMED2表达显著降低。

To discover genes that are required for embryonic development we used a forward genetic screen to identify mouse mutants that were abnormal at E9.5 and dead prior to birth. The 99J line was identified in this recessive N-Ethyl-nitrous-urea (ENU) screen and therefore the gene mutated in this line is required for normal development. 99J homozygous mutant embryos are developmentally delayed as early as E8.5 and die by E12.5. At E9.5 these mutants have a failure of chorioallantoic attachment and labyrinth development. We mapped the 99J mutation to mouse chromosome 5F and identified a single point mutation,point mutation in the first exon of transmembrane emp24 domain trafficking protein 2 (p24beta/Tmed2 herein referred to as Tmed2). This mutation results in a non-synonymous substitution of an alanine to glutamic acid in the signal sequence of TMED2. We have also found that this mutation results in a significant decrease in TMED2 expression in 99J homozygous mutant embryos.