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Loss of function of Colgalt1 disrupts collagen post-translational modification and causes musculoskeletal defects
- Source :
- Disease Models & Mechanisms, Vol 12, Iss 6 (2019)
- Publication Year :
- 2019
- Publisher :
- The Company of Biologists, 2019.
-
Abstract
- In a screen for organogenesis defects in N-ethyl-N-nitrosourea (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; here, we show that they 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.
- Subjects :
- 0301 basic medicine
Connective Tissue Disorder
GLT25D1
Myopathy
Mutant
Neuroscience (miscellaneous)
ENU
Medicine (miscellaneous)
lcsh:Medicine
General Biochemistry, Genetics and Molecular Biology
Collagenopathies
Extracellular matrix
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Immunology and Microbiology (miscellaneous)
Collagen VI
medicine
lcsh:Pathology
Zebrafish
biology
Chemistry
lcsh:R
biology.organism_classification
medicine.disease
3. Good health
Cell biology
Hydroxylysine
Collagen glycosylation
030104 developmental biology
Congenital muscular dystrophy
medicine.symptom
030217 neurology & neurosurgery
lcsh:RB1-214
Subjects
Details
- Language :
- English
- ISSN :
- 17548411 and 17548403
- Volume :
- 12
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Disease Models & Mechanisms
- Accession number :
- edsair.doi.dedup.....e54c771ed0c9e6605019e5b93f085cd4