Читать книгу Pathology of Genetically Engineered and Other Mutant Mice - Группа авторов - Страница 105

Ciliopathies affecting skeletal development most often appear as malformed ribs, polydactyly, brachydactyly, shortened long bones, and cone‐shaped epiphyses. Disruption of HH signaling regulation leads to multiple bone diseases [68] and many of the mutated genes associated with these skeletal defects encode proteins involved ciliary transport and thus HH signaling [69, 70]. SHH is a major morphogen during early stages of embryonic limb development, while IHH has a key role in endochondral ossification.

The high prevalence of skeletal and craniofacial malformations in ciliopathies [71] stems from the key role of HH signaling during the development of bone and the craniofacial complex. [72]. In both humans and mice, craniofacial malformations often manifest as micrognathia [73]. Any lines with newborn mice that show signs of impaired feeding or breathing should be carefully examined for the presence of ciliopathy‐related craniofacial malformations such as micrognathia and cleft palate. Dysfunctional HH signaling is also linked to the development of polydactyly in Bardet–Biedl, oral–facial–digital, Senior–Løken, and Meckel–Gruber syndromes, via the ciliary role in HH signaling [74]. In mice, polydactyly has been linked to mutations in IFT genes in mice [75], as primary cilia are required for cells to respond to SHH mediators [76]. Polydactyly is another ciliopathy‐related skeletal defect that should be identified in live mice or at time of necropsy.

To augment gross necropsy findings, whole‐mount skeletal staining is recommended to confirm and better characterize any suspected skeletal defects. Detailed protocols for whole‐mount skeletal staining of embryos which highlight cartilage using Alcian Blue and mineralized bone with Alizarin Red S are available [77].