Abstract: |
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/p24β1 in a mutant mouse line, 99J, identified in an ENU mutagenesis screen for recessive developmental abnormalities. This mutation does not affect Tmed2/p24β1 mRNA levels but results in loss of TMED2/p24β1 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/p24β1 is normally expressed in tissues showing morphological defects in 99J mutant embryos and that these affected tissues lack the TMED2/p24β1 oligomerization partners, TMED7/p24β3 and TMED10/p24β1. Our data reveal a requirement for TMED2/p24β1 protein in the morphogenesis of the mouse embryo and placenta. © 2010 Elsevier Inc. |
Keywords: |
controlled study; carrier protein; unclassified drug; mutation; nonhuman; animal cell; mouse; animal; metabolism; mouse mutant; mammalia; animals; mice; animal tissue; gene expression; embryo; embryo development; morphogenesis; mice, inbred c57bl; c57bl mouse; vertebrata; animal embryo; gene expression regulation; gene expression regulation, developmental; endoplasmic reticulum; messenger rna; nucleotide sequence; homozygote; embryo, mammalian; pregnancy; caenorhabditis elegans; developmental disorder; point mutation; oligomerization; placenta; placenta development; vesicular transport proteins; abnormal heart looping; er stress; p24; posterior tail bud; tmed; vesicular transport; transmembrane emp24 domain 10 protein; transmembrane emp24 domain 2 protein; transmembrane emp24 domain 7 protein; tmed10 protein, mouse; tmed2 protein, mouse; tmed7 protein, mouse; vesicular transport protein; embryo death
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