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Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/18671

Title: Over Expression of CNP Enhances the Formation of Long Bone Exostoses in Ext1+/- mice
Authors: Bukulmez, H.
Khan, F.
Bartels, C.
Fernando, C.
Esko D., J.
Warman, M. L
Keywords: Exostoses, EXT1 gene, C-type Natriuretic peptide, endochondral bone growth.
Issue Date: 2012
Citation: In process
Abstract: Multiple hereditary exostoses (MHE) is an autosomal dominant skeletal disorder caused by heterozygous loss-of-function mutations in either EXT1 or EXT2. Exostosis in patients with EXT mutations occurs at diverse skeletal sites and can undergo malignant degeneration. The exostosis in EXT1 heterozygous (EXT1+/-) mice predominantly affect the ribs and do not become malignant. In this study EXT1+/- mice were bred to transgenic mice that over-express C-type natriuretic peptide under the control of the type II collagen promoter/enhancer (CNPcol2a1TG). The purpose of this study was to determine whether CNP over expression would enhance the EXT1+/- phenotype. By itself, CNP over-expression causes skeletal overgrowth, but does not produce exostoses. EXT1+/- and CNPcol2a1TG mice were mated and 27 offspring were followed for up to 8 months. Non-rib exostoses were detected clinically and/or radiographically, and they were examined histologically following sacrifice. Eight of the 27 offspring developed non-rib exostoses and these 8 offspring were both EXT1+/- and CNPcol2a1TG positive (EXC). Of the remaining 19 mice in which we did not observe long bone or vertebral exostoses, 9 were CNPcol2a1TG, 4 were EXT1+/-, and 6 were entirely wild-type. The histological appearance of each exostosis was similar to that of human exostotic lesions. Western blots using antibodies towards NPR2 and MMP13 showed an increase in CNPcol2a1TG and EXC mice as compared to their non-transgenic littermates. There was an increase in the phosphorylated form of P38 and JNK in the EXC transgenic mice when compared to EXT and CNP mice. CNP over expression in EXT+/- mice provided the necessary environment for EXT1 haploinsufficiency for exositosis formation. EXT haploinsufficient and CNP over expressing mice provides us a new murine model to study MHE
URI: http://hdl.handle.net/123456789/18671
Appears in Collections:College of Applied Medical Sciences

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