The Heterozygous Lemd3+/GT Mouse Is Not a Murine Model for Osteopoikilosis in Humans View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2009-12

AUTHORS

Annelies Dheedene, Steven Deleye, Jan Hellemans, Steven Staelens, Stefaan Vandenberghe, Geert Mortier

ABSTRACT

Osteopoikilosis and the Buschke-Ollendorff syndrome are skeletal dysplasias with hyperostotic lesions in the long bones. These disorders are caused by heterozygous loss-of-function mutations in the LEMD3 gene. LEMD3 codes for a protein of the inner nuclear membrane that, through interaction with R-SMADs, antagonizes the BMP and TGF beta 1 pathway. It is suggested that the hyperostotic lesions in these disorders are caused by enhanced BMP and TGFbeta1 signaling. The exact mechanism by which mutations in the LEMD3 gene lead to these bone lesions has not yet been unraveled precisely. To further assess this, an Lemd3 gene-trapped mouse was created in a gene-trapping program by Baygenomics. To investigate whether the heterozygous gene-trapped mouse is a good model for osteopoikilosis in humans, we studied these mice radiologically with high-resolution micro-computed tomography (microCT) and histologically. X-ray images were evaluated by a trained radiologist, but no typical osteopoikilosis lesions could be recognized. On all microCT reconstructed images a 3D cortical and trabecular quantitative analysis was performed, investigating different histomorphometric parameters ranging from percent bone volume, bone surface/volume ratio over trabecular thickness, separation, number, and pattern factor to structure model index and fractal dimension. No significant differences were found after a t-test statistical analysis. Also, histological analysis did not reveal lesions typical for osteopoikilosis. We conclude that the heterozygous Lemd3 gene-trapped mouse is not a good model to study osteopoikilosis and the Buschke-Ollendorff syndrome. More... »

PAGES

546-551

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00223-009-9305-z

DOI

http://dx.doi.org/10.1007/s00223-009-9305-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1052896169

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19862465


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