The trafficking protein Tmed2/p24beta(1) is required for morphogenesis of the mouse embryo and placenta.
During vesicular transport between the endoplasmic reticulum and the Golgi, members of the TMED/p24 protein family form hetero-oligomeric complexes that facilitate protein-cargo recognition as well as vesicle budding. In addition, they regulate each other's level of expression. Despite analyses of TMED/p24 protein distribution in mammalian cells, yeast, and C. elegans, little is known about the role of this family in vertebrate embryogenesis. We report the presence of a single point mutation in Tmed2/p24beta(1) in a mutant mouse line, 99J, identified in an ENU mutagenesis screen for recessive developmental abnormalities. This mutation does not affect Tmed2/p24beta(1) mRNA levels but results in loss of TMED2/p24beta(1) protein. Prior to death at mid-gestation, 99J homozygous mutant embryos exhibit developmental delay, abnormal rostral-caudal elongation, randomized heart looping, and absence of the labyrinth layer of the placenta. We find that Tmed2/p24beta(1) is normally expressed in tissues showing morphological defects in 99J mutant embryos and that these affected tissues lack the TMED2/p24beta(1) oligomerization partners, TMED7/p24gamma(3) and TMED10/p24delta(1). Our data reveal a requirement for TMED2/p24beta(1) protein in the morphogenesis of the mouse embryo and placenta.
Jerome-Majewska
Loydie A
LA
Department of Pediatrics, McGill University, Montreal Children's Hospital, Montreal, Quebec, Canada. loydie.majewska@mcgill.ca
Achkar
Tala
T
Luo
Li
L
Lupu
Floria
F
Lacy
Elizabeth
E
D000818:Animals; D004622:Embryo, Mammalian / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009024:Morphogenesis; D009154:Mutation; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D033921:Vesicular Transport Proteins / Q000378:metabolism*
D008565:Membrane Proteins; C548893:Tmed10 protein, mouse; C548891:Tmed2 protein, mouse; C548892:Tmed7 protein, mouse; D033921:Vesicular Transport Proteins