Tonelli, F., Cotti, S., Leoni, L., Besio, R., Gioia, R., Marchese, L., Giorgetti, S., Villani, S., Gistelinck, C., Wagener, R., Kobbe, B., Fiedler, I. A. K., Larionova, D., Busse, B., Eyre, D., Rossi, A., Witten, P. E. and Forlino, A. (2020). Crtap and p3h1 knock out zebrafish support defective collagen chaperoning as the cause of their osteogenesis imperfecta phenotype. Matrix Biol., 90. S. 40 - 61. AMSTERDAM: ELSEVIER. ISSN 1569-1802

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Abstract

Prolyl 3-hydroxylation is a rare collagen type I post translational modification in fibrillar collagens. The primary 3Hyp substrate sites in type I collagen are targeted by an endoplasmic reticulum (ER) complex composed by cartilage associated protein (CRTAP), prolyl 3-hydroxylase 1 (P3H1) and prolyl cis/trans isomerase B, whose mutations cause recessive forms of osteogenesis imperfecta with impaired levels of alpha l (I)3Hyp986. The absence of collagen type I 3Hyp in wild type zebrafish provides the unique opportunity to clarify the role of the complex in vertebrate. Zebrafish knock outs for crtap and p3h1 were generated by CRISPR/Cas9. Mutant fish have the typical OI patients' reduced size, body disproportion and altered mineralization. Vertebral body fusions, deformities and fractures are accompanied to reduced size, thickness and bone volume. Intracellularly, collagen type I is overmodified, and partially retained causing enlarged ER cisternae. In the extracellular matrix the abnormal collagen type I assembles in disorganized fibers characterized by altered diameter. The data support the defective chaperone role of the 3-hydroxylation complex as the primary cause of the skeletal phenotype. (C) 2020 Elsevier B.V. All rights reserved.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Tonelli, F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cotti, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leoni, L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Besio, R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gioia, R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marchese, L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Giorgetti, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Villani, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gistelinck, C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wagener, R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kobbe, B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fiedler, I. A. K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Larionova, D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Busse, B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eyre, D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rossi, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Witten, P. E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Forlino, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-325397
DOI: 10.1016/j.matbio.2020.03.004
Journal or Publication Title: Matrix Biol.
Volume: 90
Page Range: S. 40 - 61
Date: 2020
Publisher: ELSEVIER
Place of Publication: AMSTERDAM
ISSN: 1569-1802
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
BASEMENT-MEMBRANE COLLAGEN; PROLYL 3-HYDROXYLATION; 3-HYDROXYPROLINE RESIDUES; DEFICIENCY; MUTATIONS; STABILITY; CLEAVAGE; PROTEIN; LETHAL; MODELMultiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/32539

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