A Ser252Trp substitution in mouse FGFR2 results in hyperplasia of embryonic salivary gland parenchyma
| Autor: | Kayoko Nakao-Kuroishi, Masahiro Mizuhara, Misa Ito-Sago, Kaori Kometani-Gunjigake, Keiji Moriyama, Kentaro Ono, Daiki Iwata, Tatsuo Kawamoto, Tsukasa Watanabe |
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| Rok vydání: | 2021 |
| Předmět: |
musculoskeletal diseases
0301 basic medicine Genetically modified mouse congenital hereditary and neonatal diseases and abnormalities Pathology medicine.medical_specialty Medicine (miscellaneous) Lumen (anatomy) Mice Transgenic Biology General Biochemistry Genetics and Molecular Biology Salivary Glands 03 medical and health sciences Mice 0302 clinical medicine Parenchyma medicine Animals Humans Receptor Fibroblast Growth Factor Type 2 General Dentistry Hyperplasia Salivary gland Fibroblast growth factor receptor 2 Fibroblast growth factor receptor 1 030206 dentistry Acrocephalosyndactylia medicine.disease Submandibular gland stomatognathic diseases 030104 developmental biology medicine.anatomical_structure embryonic structures |
| Zdroj: | Journal of oral biosciences. 63(2) |
| ISSN: | 1880-3865 |
| Popis: | Objectives Mutations in the fibroblast growth factor receptor 2 (FGFR2) gene are responsible for several severe forms of craniosynostotic disorders, such as Apert and Crouzon syndromes. Patients with craniosynostotic disorders caused by a mutation in Fgfr2 present with several clinical symptoms, including hypersalivation. Here we used a transgenic mouse model of Apert syndrome (Fgfr2+/S252W mice) to evaluate the morphology of the submandibular glands at embryonic day 15.5 (E15.5), the time point reported to mark the start of lumen formation. Methods Fgfr2+/S252W mice were generated by crossing ACTB-Cre+/+ and Fgfr2+/Neo-S252W mice. After measuring body weight, the submandibular glands were collected at E15.5. HE however, lumen formation was not affected. The mRNA expression of Fgf1, Fgfr1, Mmp2, Bmp4, Bmp7, Dusp6, and Etv5 in Fgfr2+/S252W mice was significantly higher compared to control littermates. Immunoreactivity for FGF3, FGF1, BMP4, and F4/80 was detected in the parenchyma of Fgfr2+/S252W mice. The area of apoptotic cells stained with TUNEL in Fgfr2+/S252W mice was significantly larger than that of the control littermates. Conclusions These results suggested that increased FGFR1 signaling and apoptosis in the submandibular glands of Fgfr2+/S252W mice occurred at E15.5, leading to parenchymal hyperplasia. This study demonstrated that a Ser252Trp substitution in mouse FGFR2 resulted in hyperplasia of the submandibular gland parenchyma during development. |
| Databáze: | OpenAIRE |
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