Task: Intent Identification
Input (English): During development of the vertebrate skeleton, chondrocytes form a cartilage template that is gradually replaced by bone. Hormones of the Hedgehog (HH) family have been implicated in the ossification process, but their exact relationship to normal or pathogenic bone formation is unclear. This study was undertaken to establish a genetic tool that allows the discrete inactivation of genes in spinal chondrocytes, and to investigate in vivo how chondrocyte-specific ablation of the inhibitory HH receptor Patched 1 (Ptch1) affects skeleton integrity.', 'A Cre-deleter mouse strain, mb1-Cre, for selective gene recombination in spinal chondrocytes was identified by in situ hybridization and histologic analysis. The mb1-Cre(+/-) animals were crossed with mice that harbor a loxP-flanked Ptch1 gene (Ptch1(flox/flox) ) to abrogate the inhibition of the HH signaling pathway in chondrocytes. The skeletal integrity of F1 mice was characterized by high-resolution flat-panel-based volume computed tomography and histologic staining procedures.', 'During the first weeks after birth, all mb1-Cre(+/-) /Ptch1(flox/flox) mice developed progressive spinal fusion with malformation of the vertebrae. This phenotype was caused by aberrant chondrocyte proliferation in the intervertebral discs that blocked endochondral ossification. Importantly, the disease pattern occurred in an inflammation-independent manner.
Output (English): 1