Dataset Information

Mouse cornea,sclera,skin LC-MSMS

ABSTRACT: We generated a P4ha2 knock-out mouse line (C57BL/6) by using CRISPR-Cas9 system. By mass spectrum, reduced proline hydroxylation was observed in collagens isolated from skin, sclera and cornea of P4ha2-/- mice.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cornea, Skin, Sclera

SUBMITTER: Yanling Liu

LAB HEAD: Zhengmao Hu

PROVIDER: PXD023006 | Pride | 2026-03-02

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

Items per page:

1 - 5 of 21

Publications

P4HA2 Participates in Pathogenesis of Refractive Error by Regulating Collagen Posttranslational Modification and Extracellular Matrix Balance.

Liu Yanling Y Dong Shanshan S Huang Furong F Li Ruotong R He Xi X Jiang Yizheng Y Tian Qi Q Xiong Haofeng H Jin Liangyun L Wang Qiongsi Q Xia Lu L Chen Jingjing J Wu Huidan H Guo Hui H Zhou Xiangtian X Xia Kun K Hu Zhengmao Z

Human mutation 20260225

Myopia represents a refractive anomaly characterized by impaired vision resulting from a misfocused image in front of the fovea. Although numerous genes linked to high myopia (HM) have been identified, the exact etiology and pathogenesis mechanisms of HM remain predominantly obscure. In a prior investigation, a mutation in the P4HA2 gene was identified in association with HM. To illuminate the potential mechanisms of action of P4HA2 in HM, we established a P4HA2-knockout mou ...[more]

PMID: 41756678

Similar Datasets

Project description:Type I collagen is the main structural protein in mammals and other vertebrate life forms. During the biosynthesis of collagens, prolyl-3-hydroxylase 1 (P3H1) catalyzes 3-hydroxylation of proline residues and acts as a chaperone. Deficiency of P3H1 causes Osteogenesis Imperfecta (OI), a hereditary disorder primarily associated with mutations in type I collagen and collagen-related genes. However, the full impact of P3H1 deficiency on the collagen biosynthesis machinery and post-translational modifications (PTMs) is not known. In this comprehensive study, we conducted a detailed investigation of P3h1 knockout mice collagen by performing amino acid analysis, high-resolution tandem mass spectrometry (MS/MS)-based identification and site-specific quantification of collagen PTMs, and gene expression analysis to unravel the impact of P3H1 deficiency on type I collagen biosynthesis in mouse tail tendon. Amino acid analysis revealed a general overmodification of prolines and lysines in mouse tendon type I collagen. Site-specific MS/MS-based quantification of collagen PTMs verified the P3H1-dependent 3-hydroxyproline sites COL1A1-P1153 and COL1A2-P803, but demonstrated frequent overhydroxylation of prolines, including 3- and 4-hydroxylation, as well as increased 5-hydroxylation of lysines in unprecedented detail. Gene expression analysis in P3H1-deficient mouse tail tenocytes unveiled upregulation of Col1a1 expression along with several other genes encoding collagen biosynthetic enzymes. Interestingly, upregulation of P4ha2 expression stood out and correlated with specific overhydroxylation of prolyl-4-hydroxylation sites containing the P4HA2 preferred motif EPG. In summary, the loss of P3H1 led to a profound imbalance in the entire ER-resident collagen biosynthetic machinery and drastically altered the collagen I PTM network. In conclusion, our findings offer a novel mechanism underlying overmodification in addition to prolonged exposure of unfolded collagen chains in the ER, suggest the presence of so far unknown feedback mechanisms between ER-resident collagen biosynthesis and collagen biosynthetic gene expression, and further emphasize the essential role of P3H1 in maintaining collagen quality control.

			Action	DRS
	WT_20gong_2020181227.mgf	Mgf
	WT_gong_20181227.wiff	Wiff
	WT_gong_20181227.wiff.scan	Wiff
	WT_jiao_20181227.mgf	Mgf
	WT_jiao_20181227.wiff	Wiff