Mutation of a ubiquitously expressed mouse transmembrane protein (Tapt1) causes specific skeletal homeotic transformations.
L5Jcs1 is a perinatal lethal mutation uncovered in a screen for ENU-induced mutations on mouse chromosome 5. L5Jcs1 homozygotes exhibit posterior-to-anterior transformations of the vertebral column midsection, similar to mice deficient for Hoxc8 and Hoxc9. Positional cloning efforts identified a mutation in a novel, evolutionarily conserved, and ubiquitously expressed gene dubbed Tapt1 (Transmembrane anterior posterior transformation 1). TAPT1 is predicted to contain several transmembrane domains, and part of the gene is orthologous to an unusual alternatively spliced human transcript encoding the cytomegalovirus gH receptor. We speculate that TAPT1 is a downstream effector of HOXC8 that may act by transducing or transmitting extracellular information required for axial skeletal patterning during development.
Howell
Gareth R
GR
The Jackson Laboratory, Bar Harbor, Maine 04660, USA.
Shindo
Mami
M
Murray
Stephen
S
Gridley
Thomas
T
Wilson
Lawriston A
LA
Schimenti
John C
JC
D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D001842:Bone and Bones / Q000002:abnormalities*; D033481:Chromosomes, Mammalian / Q000235:genetics; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D004622:Embryo, Mammalian / Q000002:abnormalities; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D019683:Penetrance; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000378:metabolism
D018398:Homeodomain Proteins; C489816:Hoxc8 protein, mouse; D008565:Membrane Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C519229:TAPT1 protein, mouse; D014759:Viral Envelope Proteins; C071440:glycoprotein H, Cytomegalovirus