Protein trafficking during placental development: the role of TMED2

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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.