Skeletal Deformities in Osterix-Cre;Tgfbr2f/f Mice May Cause Postnatal Death
| Autor: | Monica Stanwick, Andrew Kruggel, Sarah B. Peters, Kara N. Corps, Juliann Rectenwald |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Mesenchyme Cre recombinase Osterix-Cre Calvaria Case Report Biology QH426-470 osteochondral dysplasia 03 medical and health sciences 0302 clinical medicine Internal medicine Conditional gene knockout medicine Genetics conditional knockout mouse models off-target Cre Receptor Genetics (clinical) Gastrointestinal tract postnatal musculoskeletal neural and ocular physiology Hypoxia (medical) 030104 developmental biology medicine.anatomical_structure Endocrinology TGFbeta bone development 030220 oncology & carcinogenesis medicine.symptom Transforming growth factor |
| Zdroj: | Genes Genes, Vol 12, Iss 975, p 975 (2021) |
| ISSN: | 2073-4425 |
| Popis: | Transforming growth factor β (TGFβ) signaling plays an important role in skeletal development. We previously demonstrated that the loss of TGFβ receptor II (Tgfbr2) in Osterix-Cre-expressing mesenchyme results in defects in bones and teeth due to reduced proliferation and differentiation in pre-osteoblasts and pre-odontoblasts. These Osterix-Cre;Tgfbr2f/f mice typically die within approximately four weeks for unknown reasons. To investigate the cause of death, we performed extensive pathological analysis on Osterix-Cre- (Cre-), Osterix-Cre+;Tgfbr2f/wt (HET), and Osterix-Cre+;Tgfbr2f/f (CKO) mice. We also crossed Osterix-Cre mice with the ROSA26mTmG reporter line to identify potential off-target Cre expression. The findings recapitulated published skeletal and tooth abnormalities and revealed previously unreported osteochondral dysplasia throughout both the appendicular and axial skeletons in the CKO mice, including the calvaria. Alterations to the nasal area and teeth suggest a potentially reduced capacity to sense and process food, while off-target Cre expression in the gastrointestinal tract may indicate an inability to absorb nutrients. Additionally, altered nasal passages and unexplained changes in diaphragmatic muscle support the possibility of hypoxia. We conclude that these mice likely died due to a combination of breathing difficulties, malnutrition, and starvation resulting primarily from skeletal deformities that decreased their ability to sense, gather, and process food. |
| Databáze: | OpenAIRE |
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