Watanabe H, Nakata K, Kimata K, Nakanishi I, Yamada Y
Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892-4370, USA.
Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):6943-7. doi: 10.1073/pnas.94.13.6943.
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.
小鼠软骨基质缺乏症（cmd）是一种常染色体隐性疾病，由软骨中一种大型硫酸软骨素蛋白聚糖——聚集蛋白聚糖的基因缺陷引起。纯合子（-/-）的特征是腭裂以及四肢、尾巴和口鼻短小。它们出生后不久因呼吸衰竭而死亡，杂合子（+/-）出生时看起来正常。在此我们报告，杂合子表现出侏儒症，并随着年龄增长出现脊柱排列不齐。在19个月龄内，它们因颈椎排列不齐而出现痉挛性步态，并因饥饿而死亡。组织学检查显示椎间盘突出和退变的发生率很高。电子显微镜检查显示杂合子中椎间盘软骨细胞发生退变。这些发现可能有助于识别易患脊柱退变的人类突变。
