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在E9.5时异常并在出生前死亡的小鼠突变体。 在该隐性N-乙基亚硝基脲（ENU）筛选中鉴定了99 J系，因此该系中突变的基因是正常发育所需的。 99 J纯合突变胚胎早在E8.5就发育延迟，并在E12.5死亡。 在E9.5，这些突变体具有绒毛尿囊附着和迷路发育的失败。 我们将99 J突变定位于小鼠染色体5 F，并鉴定了单点突变，即跨膜emp 24结构域运输蛋白2（p24 β/Tmed 2，本文称为Tmed 2）的第一外显子中的点突变。 该突变导致TMED 2的信号序列中丙氨酸非同义取代为谷氨酸。 我们还发现，这种突变导致99 J纯合突变胚胎中TMED 2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.