title: Early postnatal death and motor disorders in mice congenitally deficient in calnexin expression.
abstract: Calnexin is a ubiquitously expressed type I membrane protein which is exclusively localized in the endoplasmic reticulum (ER). In mammalian cells, calnexin functions as a chaperone molecule and plays a key role in glycoprotein folding and quality control within the ER by interacting with folding intermediates via their monoglucosylated glycans. In order to gain more insight into the physiological roles of calnexin, we have generated calnexin gene-deficient mice. Despite its profound involvement in protein folding, calnexin is not essential for mammalian-cell viability in vivo: calnexin gene knockout mice were carried to full term, although 50% died within 48 h and the majority of the remaining mice had to be sacrificed within 4 weeks, with only a very few mice surviving to 3 months. Calnexin gene-deficient mice were smaller than their littermates and showed very obvious motor disorders, associated with a dramatic loss of large myelinated nerve fibers. Thus, the critical contribution of calnexin to mammalian physiology is tissue specific.
authors.affiliation: Imperial Cancer Research Fund, Academic Department of Histopathology, Bart's and the Queen Mary's School of Medicine and Dentistry, Whitechapel, United Kingdom. angela.denzel@kcl.ac.uk.
authors.forename: Angela
authors.initials: A
authors.lastname: Denzel
authors.forename: Maurizio
authors.initials: M
authors.lastname: Molinari
authors.forename: Cesar
authors.initials: C
authors.lastname: Trigueros
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Martin
authors.forename: Shanti
authors.initials: S
authors.lastname: Velmurgan
authors.forename: Sue
authors.initials: S
authors.lastname: Brown
authors.forename: Gordon
authors.initials: G
authors.lastname: Stamp
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
mesh_terms: D000483:Alleles; D000818:Animals; D000831:Animals, Newborn; D037281:Calnexin / Q000235:genetics* / Q000502:physiology*; D002470:Cell Survival; D004622:Embryo, Mammalian / Q000166:cytology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006579:Heterozygote; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D008957:Models, Genetic; D018832:Molecular Chaperones; D009046:Motor Neurons / Q000473:pathology*; D009186:Myelin Sheath / Q000473:pathology; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D010641:Phenotype; D017510:Protein Folding; D011995:Recombination, Genetic; D013234:Stem Cells / Q000166:cytology; D013997:Time Factors; D014162:Transfection
chemical_list: D018832:Molecular Chaperones; D037281:Calnexin