title: Dwarfism and age-associated spinal degeneration of heterozygote cmd mice defective in aggrecan.
abstract: 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.
authors.affiliation: Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892-4370, USA.
authors.forename: H
authors.initials: H
authors.lastname: Watanabe
authors.forename: K
authors.initials: K
authors.lastname: Nakata
authors.forename: K
authors.initials: K
authors.lastname: Kimata
authors.forename: I
authors.initials: I
authors.lastname: Nakanishi
authors.forename: Y
authors.initials: Y
authors.lastname: Yamada
mesh_terms: D053674:Aggrecans; D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002357:Cartilage Diseases / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D004392:Dwarfism / Q000235:genetics* / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D006579:Heterozygote; D037181:Lectins, C-Type; D051379:Mice; D008817:Mice, Mutant Strains; D011509:Proteoglycans / Q000172:deficiency / Q000235:genetics*; D013116:Spinal Cord / Q000002:abnormalities*
chemical_list: C508320:Acan protein, mouse; D053674:Aggrecans; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D011509:Proteoglycans