Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

The Ptch1(DL) mouse: a new model to study lambdoid craniosynostosis and basal cell nevus syndrome-associated skeletal defects.

Authors: Feng, Weiguo  Choi, Irene  Clouthier, David E  Niswander, Lee  Williams, Trevor 
Citation: Feng W, etal., Genesis. 2013 Oct;51(10):677-89. doi: 10.1002/dvg.22416. Epub 2013 Aug 30.
Pubmed: (View Article at PubMed) PMID:23897749
DOI: Full-text: DOI:10.1002/dvg.22416

Mouse models provide valuable opportunities for probing the underlying pathology of human birth defects. By using an N-ethyl-N-nitrosourea-based screen for recessive mutations affecting craniofacial anatomy, we isolated a mouse strain, Dogface-like (DL), with abnormal skull and snout morphology. Examination of the skull indicated that these mice developed craniosynostosis of the lambdoid suture. Further analysis revealed skeletal defects related to the pathology of basal cell nevus syndrome (BCNS) including defects in development of the limbs, scapula, ribcage, secondary palate, cranial base, and cranial vault. In humans, BCNS is often associated with mutations in the Hedgehog receptor PTCH1 and genetic mapping in DL identified a point mutation at a splice donor site in Ptch1. By using genetic complementation analysis we determined that DL is a hypomorphic allele of Ptch1, leading to increased Hedgehog signaling. Two aberrant transcripts are generated by the mutated Ptch1(DL) gene, which would be predicted to reduce significantly the levels of functional Patched1 protein. This new Ptch1 allele broadens the mouse genetic reagents available to study the Hedgehog pathway and provides a valuable means to study the underlying skeletal abnormalities in BCNS. In addition, these results strengthen the connection between elevated Hedgehog signaling and craniosynostosis.

Annotation

Disease Annotations
Objects Annotated

Additional Information

 
CRRD Object Information
CRRD ID: 13207424
Created: 2017-07-28
Species: All species
Last Modified: 2017-07-28
Status: ACTIVE



NHLBI Logo

RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.