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PMID: 9524110 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Mice deficient for the secreted glycoprotein SPARC/osteonectin/BM40 develop normally but show severe age-onset cataract formation and disruption of the lens.

The EMBO journal ·Vol. 17 ·No. 7 ·1998-04-01 ·Pages 1860-70

Gilmour DT, Lyon GJ, Carlton MB, Sanes JR, Cunningham JM, Anderson JR, Hogan BL, Evans MJ, Colledge WH

Abstract

SPARC (secreted protein acidic and rich in cysteine, also known as osteonectin/BM40) is a secreted Ca2+-binding glycoprotein that interacts with a range of extracellular matrix molecules, including collagen IV. It is widely expressed during embryogenesis, and in vitro studies have suggested roles in the regulation of cell adhesion and proliferation, and in the modulation of cytokine activity. In order to analyse the function of this protein in vivo, the endogenous Sparc locus was disrupted by homologous recombination in murine embryonic stem cells. SPARC-deficient mice (Sparctm1Cam) appear normal and fertile until around 6 months of age, when they develop severe eye pathology characterized by cataract formation and rupture of the lens capsule. The first sign of lens pathology occurs in the equatorial bow region where vacuoles gradually form within differentiating epithelial cells and fibre cells. The lens capsule, however, shows no qualitative changes in the major basal lamina proteins laminin, collagen IV, perlecan or entactin. These mice are an excellent resource for further studies on how SPARC affects cell behaviour in vivo.

MeSH Terms
Age of Onset Animals Bone and Bones Cataract/embryology,genetics,pathology Embryonic and Fetal Development Epithelial Cells Extracellular Matrix Proteins/analysis Gene Expression Regulation, Developmental Lens Capsule, Crystalline/chemistry,ultrastructure Lens, Crystalline/pathology Male Mice Mice, Knockout Osteonectin/analysis,genetics,physiology RNA, Messenger/analysis Testis/chemistry
Chemicals
Extracellular Matrix Proteins Osteonectin RNA, Messenger
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Gilmour D T
Wellcome/CRC Institute of Cancer and Developmental Biology and Department of Genetics, University of Cambridge, Tennis Court Rd, Cambridge CB2 3QR.
Lyon G J
Carlton M B
Sanes J R
Cunningham J M
Anderson J R
Hogan B L
Evans M J
Colledge W H
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/17.7.1860
Published
1998-04-01
Pages
1860-70
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1170533
Subset
IM
Grants
Wellcome Trust · United Kingdom
External Links
PubMed source DOI: 10.1093/emboj/17.7.1860 PMC Full Text View journal details
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