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Aggrecan 1 expression in Dmm mice
Author(s) -
Niederhauser Cindy Marie,
Montaño Carolina,
Bomsta Brandon D.,
Seegmiller Robert E.,
Sudweeks Sterling N.,
Bridgewater Laura C.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a545-c
Subject(s) - aggrecan , proteoglycan , cartilage , type ii collagen , extracellular matrix , chemistry , microbiology and biotechnology , chondrocyte , endoplasmic reticulum , biology , anatomy , pathology , medicine , osteoarthritis , articular cartilage , alternative medicine
Type II collagen is a major component of the cartilage extra‐cellular matrix (ECM). The Disproportionate micromelia ( Dmm ) mouse contains a mutation in the C‐terminal coding region of the type II collagen gene, Col2a1. This mutation causes severe skeletal abnormalities and is lethal in homozygotes ( Dmm/Dmm ). It also causes dwarfism in heterozygotes ( Dmm/+ ). In Dmm/Dmm mice, type II collagen is retained in the endoplasmic reticulum (ER) of chondrocytes and is absent from the ECM. The structure of the ECM is severely disorganized. Dmm/+ mutants also show some accumulation of type II collagen in the ER, and the total amount of ECM is reduced, but the organization of collagen fibrils in the ECM appears relatively normal. This suggests that secretion of the proteoglycan components of the ECM in Dmm /+ mice is reduced in proportion to type II collagen. To identify a mechanism for this suppression, we used immunohistochemistry to determine whether aggrecan (a major component of cartilage proteoglycan) is retained in the ER of Dmm /+ fetal rib cartilage. We also used RT‐PCR to determine whether aggrecan transcription is reduced. Aggrecan protein was not found to be abnormally retained in the ER. Transcription of the aggrecan gene, however, was reduced to one‐third of wild‐type in these cells. These results suggest that aggrecan levels in the cartilage of Dmm /+ mice are regulated by a feedback mechanism that acts at the level of transcription to maintain a correct ratio of proteoglycan to collagen. Funding through NIH AR048839.