Genotype-Phenotype Correlation of Tracheal Cartilaginous Sleeves and Fgfr2 Mutations in Mice.

TitleGenotype-Phenotype Correlation of Tracheal Cartilaginous Sleeves and Fgfr2 Mutations in Mice.
Publication TypeJournal Article
Year of Publication2021
AuthorsLam AS, Liu CC, Deutsch GH, Rivera J, Perkins JA, Holmes G, Jabs EW, Cunningham ML, Dahl JP
Date Published2021 04
KeywordsAcanthosis Nigricans, Acrocephalosyndactylia, Animals, Cartilage, Craniofacial Dysostosis, Craniosynostoses, Disease Models, Animal, Ear, Genetic Association Studies, Humans, Mice, Mutation, Phenotype, Receptor, Fibroblast Growth Factor, Type 2, Scalp Dermatoses, Skin Abnormalities, Trachea, Tracheal Diseases, X-Ray Microtomography

OBJECTIVES: To characterize tracheal cartilage morphology in mouse models of fibroblast growth factor receptor (Fgfr2)-related craniosynostosis syndromes. To establish relationships between specific Fgfr2 mutations and tracheal cartilaginous sleeve (TCS) phenotypes in these mouse models.

METHODS: Postnatal day 0 knock-in mouse lines with disease-specific genetic variations in the Fgfr2 gene (Fgfr2 , Fgfr2 , Fgfr2 , Fgfr2 , and Fgfr2 ) as well as line-specific controls were utilized. Tracheal cartilage morphology as measured by gross analyses, microcomputed tomography (μCT), and histopathology were compared using Chi-squared and single-factor analysis of variance statistical tests.

RESULTS: A greater proportion of rings per trachea were abnormal in Fgfr2 tracheas (63%) than Fgfr2 (17%), Fgfr2 (17%), Fgfr2 (12%), and controls (10%) (P < .001 for each vs. Fgfr2 ). TCS segments were found only in Fgfr2 (100%) and Fgfr2 (72%) tracheas. Cricoid and first-tracheal ring fusion was noted in all Fgfr2 and 94% of Fgfr2 samples. The Fgfr2 and Fgfr2 groups were found to have greater areas and volumes of cartilage than other lines on gross analysis and μCT. Histologic analyses confirmed TCS among the Fgfr2 and Fgfr2 groups, without appreciable differences in cartilage morphology, cell size, or density; no histologic differences were observed among other Fgfr2 lines compared to controls.

CONCLUSION: This study found TCS phenotypes only in the Fgfr2 mouse lines. These lines also had increased tracheal cartilage compared to other mutant lines and controls. These data support further study of the Fgfr2 mouse lines and the investigation of other Fgfr2 variants to better understand their role in tracheal development and TCS formation.

LEVEL OF EVIDENCE: NA Laryngoscope, 131:E1349-E1356, 2021.

Alternate JournalLaryngoscope
PubMed ID32886384
PubMed Central IDPMC7930142
Grant ListP01 HD078233 / HD / NICHD NIH HHS / United States
P50 HD103524 / HD / NICHD NIH HHS / United States
R01 DE022988 / DE / NIDCR NIH HHS / United States
T32 DC000018 / DC / NIDCD NIH HHS / United States
Faculty Reference: 
Che Carrie Liu, MD, MPH