ZFIN ID: ZDB-PUB-190519-2
Loss of function of Colgalt1 disrupts collagen post-translational modification and causes musculoskeletal defects
Geister, K.A., Lopez-Jimenez, A.J., Houghtaling, S., Ho, T.H., Vanacore, R., Beier, D.R.
Date: 2019
Source: Disease models & mechanisms   12(6): (Journal)
Registered Authors: Beier, David R.
Keywords: Collagen glycosylation, Collagenopathies, ENU, Myopathy
MeSH Terms:
  • Alleles
  • Animals
  • Collagen/metabolism*
  • Embryo, Mammalian/pathology
  • Extracellular Matrix/metabolism
  • Fibroblasts/metabolism
  • Fibroblasts/pathology
  • Galactosyltransferases/deficiency*
  • Galactosyltransferases/metabolism
  • Glycosylation
  • Loss of Function Mutation/genetics*
  • Mice
  • Molecular Weight
  • Muscles/metabolism
  • Muscles/pathology
  • Musculoskeletal System/pathology*
  • Mutation, Missense/genetics
  • Phenotype
  • Protein Processing, Post-Translational*
  • Skin/metabolism
  • Skin/pathology
  • Zebrafish
  • Zebrafish Proteins/metabolism*
PubMed: 31101663 Full text @ Dis. Model. Mech.
In a screen for organogenesis defects in ENU-induced mutant mice, we discovered a line carrying a mutation in Colgalt1 (collagen (beta 1-O) galactosyltransferase type 1), which is required for proper galactosylation of hydroxylysine residues in a number of collagens. Colgalt1 mutant embryos have not been previously characterized and exhibit skeletal and muscular defects. Analysis of mutant-derived embryonic fibroblasts reveals that COLGALT1 acts on collagen IV and VI, and, while collagen VI appears stable and its secretion is not affected, collagen IV accumulates inside of cells and within the extracellular matrix, possibly due to instability and increased degradation. We also generated mutant zebrafish that do not express the duplicated orthologs of mammalian Colgalt1 The double homozygote mutants have muscle defects; they are viable through the larvae stage but do not survive to 10 days post-fertilization. We hypothesize that the Colgalt1 mutant could serve as a model of a human connective tissue disorder and/or congenital muscular dystrophy or myopathy.