Defective bone formation in Krox-20 mutant mice.
Defective bone formation in Krox-20 mutant mice.
复制标题
Krox-20 突变小鼠的骨形成缺陷。
作者：
G. Levi;P. Topilko;S. Schneider;Marco Lasagna;S. Mantero;R. Cancedda;P. Charnay
软骨内骨化是脊椎动物骨骼形成的普遍模式;它开始于胚胎发育期间，当长骨的软骨模型发育成肥大的中心区域时，其被骨小梁和骨髓取代。尽管有几种转录因子与四肢和中轴骨骼的图案形成有关，但人们对骨骼形成中涉及的转录调节知之甚少。我们在小鼠Krox-20基因中创建了一个无效等位基因，该基因编码锌指转录因子，通过在E. coli lacZ基因的表达，并显示Krox-20-/-胚胎的后脑分割和周围神经髓鞘形成受到影响。我们在这里报告说，Krox-20也被激活的一个亚群的生长板肥大软骨细胞和分化成骨细胞，它的破坏严重影响endochondrialossification。Krox-20-/-小鼠出现骨骼异常，包括新形成的骨的长度和厚度减少，钙化骨小梁急剧减少和严重的多孔性。在纯合突变体中，骨形成和钙化的骨膜成分似乎不受影响，这表明Krox-20的主要作用是控制肥大软骨细胞-成骨细胞相互作用，导致骨内膜骨形成。
Endochondral ossification is the prevalent mode of vertebrate skeleton formation; it starts during embryogenesis when cartilage models of long bones develop central regions of hypertrophy which are replaced by bony trabeculae and bone marrow. Although several transcription factors have been implicated in pattern formation in the limbs and axial skeleton, little is known about the transcriptional regulations involved in bone formation. We have created a null allele in the mouse Krox-20 gene, which encodes a zinc finger transcription factor, by in frame insertion of the E. coli lacZ gene and shown that hindbrain segmentation and peripheral nerve myelination are affected in Krox-20-/- embryos. We report here that Krox-20 is also activated in a subpopulation of growth plate hypertrophic chondrocytes and in differentiating osteoblasts and that its disruption severely affects endochondral ossification. Krox-20-/- mice develop skeletal abnormalities including a reduced length and thickness of newly formed bones, a drastic reduction of calcified trabeculae and severe porosity. The periosteal component to bone formation and calcification does not appear to be affected in the homozygous mutant suggesting that the major role for Krox-20 is to be found in the control of the hypertrophic chondrocyte-osteoblast interactions leading to endosteal bone formation.
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DOI：
--
发表时间：
1994
期刊：
Development (Cambridge, England). Supplement
影响因子：
--
作者：
Bruce A. Morgan;Clifford J. Tabin
通讯作者：
Bruce A. Morgan;Clifford J. Tabin
影响因子：
10.5
作者：
KARAPLIS, AC;LUZ, A;MULLIGAN, RC
通讯作者：
MULLIGAN, RC
影响因子：
56.9
作者：
MILBRANDT, J
通讯作者：
MILBRANDT, J
DOI：
10.1073/pnas.85.21.7857
发表时间：
1988-11-01
影响因子：
11.1
作者：
CHRISTY, BA;LAU, LF;NATHANS, D
通讯作者：
NATHANS, D