Dwarfism and age-associated spinal degeneration of heterozygote cmd mice defective in aggrecan
Open accessAbstract
Mouse cartilage matrix deficiency ( cmd ) is an autosomal recessive disorder caused by a genetic defect of aggrecan, a large chondroitin sulfate proteoglycan in cartilage. The homozygotes (−/−) are characterized by cleft palate and short limbs, tail, and snout. They die just after birth because of respiratory failure, and the heterozygotes (+/−) appear normal at birth. Here we report that the heterozygotes show dwarfism and develop spinal misalignment with age. Within 19 months of age, they exhibit spastic gait caused by misalignment of the cervical spine and die because of starvation. Histological examination revealed a high incidence of herniation and degeneration of vertebral discs. Electron microscopy showed a degeneration of disc chondrocytes in the heterozygotes. These findings may facilitate the identification of mutations in humans predisposed to spinal degeneration.
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ACAN+/− mice are aggrecan-deficient.
“heterozygote aggrecan-deficient (ACAN+/−) mice”
From Aggrecan, link protein and tenascin-R are essential components of the perineuronal net to protect neurons against iron-induced oxidative stress (2014) · cites this paper as [54]
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- Authors
- Watanabe, H., Nakata, K., Kimata, K., Nakanishi, I., & Yamada, Y.
- Affiliations
- Kanazawa University (JP)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1997-06-24
- Volume
- 94
- Issue
- 13
- Pages
- 6943-6947
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC21264
- OpenAlex
- W2025950270
- Cited by
- 156
- References
- 26
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 2 · 2022: 9 · 2021: 4 · 2020: 5 · 2019: 3 · 2018: 6 · 2017: 6 · 2016: 4 · 2015: 3 · 2014: 6 · 2013: 5 · 2012: 6
- FWCI
- 3.02
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
- Keywords
- aggrecan, heterozygous mice, dwarfism, spastic gait, disc herniation, intervertebral disc degeneration, chondroitin sulfate proteoglycans
- MeSH terms
- Aging, Animals, Cartilage Diseases, Dwarfism, Heterozygote, Mice, Mutant Strains, Proteoglycans, Spinal Cord, Extracellular Matrix Proteins, Lectins, C-Type, Mice, Aggrecans
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