Crouzon syndrome mouse model exhibits cartilage hyperproliferation and defective segmentation in the developing trachea.

Autor: Hines EA; Laboratory of Genetics, University of Wisconsin, Madison, WI, 53706, USA., Jones MN; Laboratory of Genetics, University of Wisconsin, Madison, WI, 53706, USA., Harvey JF; Laboratory of Genetics, University of Wisconsin, Madison, WI, 53706, USA., Perlyn C; Department of Surgery, Florida International University College of Medicine, Miami, FL, 33199, USA., Ornitz DM; Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, 63110, USA., Sun X; Laboratory of Genetics, University of Wisconsin, Madison, WI, 53706, USA. xinsun@ucsd.edu.; Department of Pediatrics, University of California-San Diego, La Jolla, CA, 92093, USA. xinsun@ucsd.edu., Verheyden JM; Laboratory of Genetics, University of Wisconsin, Madison, WI, 53706, USA. jverheyden@ucsd.edu.; Department of Pediatrics, University of California-San Diego, La Jolla, CA, 92093, USA. jverheyden@ucsd.edu.
Jazyk: angličtina
Zdroj: Science China. Life sciences [Sci China Life Sci] 2019 Oct; Vol. 62 (10), pp. 1375-1380. Date of Electronic Publication: 2019 Aug 26.
DOI: 10.1007/s11427-019-9568-x
Abstrakt: Crouzon syndrome is the result of a gain-of-function point mutation in FGFR2. Mimicking the human mutation, a mouse model of Crouzon syndrome (Fgfr 2342Y ) recapitulates patient deformities, including failed tracheal cartilage segmentation, resulting in a cartilaginous sleeve in the homozygous mutants. We found that the Fgfr2 C342Y/C342Y mutants exhibited an increase in chondrocytes prior to segmentation. This increase is due at least in part to over proliferation. Genetic ablation of chondrocytes in the mutant led to restoration of segmentation in the lateral but not central portion of the trachea. These results suggest that in the Fgfr2 C342Y/C342Y mutants, increased cartilage cell proliferation precedes and contributes to the disruption of cartilage segmentation in the developing trachea.
Databáze: MEDLINE
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