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Skeletal Deformities in Osterix-Cre;Tgfbr2(f/f) Mice May Cause Postnatal Death

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-oste...

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Autores principales: Corps, Kara, Stanwick, Monica, Rectenwald, Juliann, Kruggel, Andrew, Peters, Sarah B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307487/
https://www.ncbi.nlm.nih.gov/pubmed/34202311
http://dx.doi.org/10.3390/genes12070975
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author Corps, Kara
Stanwick, Monica
Rectenwald, Juliann
Kruggel, Andrew
Peters, Sarah B.
author_facet Corps, Kara
Stanwick, Monica
Rectenwald, Juliann
Kruggel, Andrew
Peters, Sarah B.
author_sort Corps, Kara
collection PubMed
description 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;Tgfbr2(f/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+;Tgfbr2(f/wt) (HET), and Osterix-Cre+;Tgfbr2(f/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.
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spelling pubmed-83074872021-07-25 Skeletal Deformities in Osterix-Cre;Tgfbr2(f/f) Mice May Cause Postnatal Death Corps, Kara Stanwick, Monica Rectenwald, Juliann Kruggel, Andrew Peters, Sarah B. Genes (Basel) Case Report 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;Tgfbr2(f/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+;Tgfbr2(f/wt) (HET), and Osterix-Cre+;Tgfbr2(f/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. MDPI 2021-06-25 /pmc/articles/PMC8307487/ /pubmed/34202311 http://dx.doi.org/10.3390/genes12070975 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Corps, Kara
Stanwick, Monica
Rectenwald, Juliann
Kruggel, Andrew
Peters, Sarah B.
Skeletal Deformities in Osterix-Cre;Tgfbr2(f/f) Mice May Cause Postnatal Death
title Skeletal Deformities in Osterix-Cre;Tgfbr2(f/f) Mice May Cause Postnatal Death
title_full Skeletal Deformities in Osterix-Cre;Tgfbr2(f/f) Mice May Cause Postnatal Death
title_fullStr Skeletal Deformities in Osterix-Cre;Tgfbr2(f/f) Mice May Cause Postnatal Death
title_full_unstemmed Skeletal Deformities in Osterix-Cre;Tgfbr2(f/f) Mice May Cause Postnatal Death
title_short Skeletal Deformities in Osterix-Cre;Tgfbr2(f/f) Mice May Cause Postnatal Death
title_sort skeletal deformities in osterix-cre;tgfbr2(f/f) mice may cause postnatal death
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307487/
https://www.ncbi.nlm.nih.gov/pubmed/34202311
http://dx.doi.org/10.3390/genes12070975
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