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A mouse model for achondroplasia produced by targeting fibroblast growth factor receptor 3
Year:
1999
Authors :
Pines, Mark
;
.
Volume :
96
Co-Authors:
Wang, Y., Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100, Israel
Spatz, M.K., Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100, Israel
Kannan, K., Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100, Israel
Hayk, H., Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100, Israel
Avivi, A., Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100, Israel
Gorivodsky, M., Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, 76100, Israel
Pines, M., Institute of Animal Science, Agricultural Research Organization, Volcani Center, Bet Dagan, 50250, Israel
Yayon, A., Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100, Israel
Lonai, P., Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, 76100, Israel
Givol, D., Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100, Israel
Facilitators :
From page:
4455
To page:
4460
(
Total pages:
6
)
Abstract:
Achondroplasia, the most common form of dwarfism in man, is a dominant genetic disorder caused by a point mutation (G380R) in the transmembrane region of fibroblast growth factor receptor 3 (FGFR3). We used gene targeting to introduce the human achondroplasia mutation into the murine FGFR3 gene. Heterozygotes for this point mutation that carried the neo cassette were normal whereas neo+ homozygotes had a phenotype similar to FGFR3-deficient mice, exhibiting bone overgrowth. This was because of interference with mRNA processing in the presence of the neo cassette. Removal of the neo selection marker by Cre/loxP recombination yielded a dominant dwarf phenotype. These mice are distinguished by their small size, shortened craniofacial area, hypoplasia of the midface with protruding incisors, distorted brain case with anteriorly shifted foramen magnum, kyphosis, and narrowed and distorted growth plates in the long bones, vertebrae, and ribs. These experiments demonstrate that achondroplasia results from a gain-of FGFR3-function leading to inhibition of chondrocyte proliferation. These achondroplastic dwarf mice represent a reliable and useful model for developing drugs for potential treatment of the human disease.
Note:
Related Files :
animal experiment
Animals
Cell Proliferation
Growth plate
mice
Murinae
RNA processing
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More details
DOI :
10.1073/pnas.96.8.4455
Article number:
Affiliations:
Database:
Scopus
Publication Type:
article
;
.
Language:
English
Editors' remarks:
ID:
21545
Last updated date:
02/03/2022 17:27
Creation date:
16/04/2018 23:45
Scientific Publication
A mouse model for achondroplasia produced by targeting fibroblast growth factor receptor 3
96
Wang, Y., Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100, Israel
Spatz, M.K., Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100, Israel
Kannan, K., Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100, Israel
Hayk, H., Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100, Israel
Avivi, A., Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100, Israel
Gorivodsky, M., Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, 76100, Israel
Pines, M., Institute of Animal Science, Agricultural Research Organization, Volcani Center, Bet Dagan, 50250, Israel
Yayon, A., Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100, Israel
Lonai, P., Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, 76100, Israel
Givol, D., Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100, Israel
A mouse model for achondroplasia produced by targeting fibroblast growth factor receptor 3
Achondroplasia, the most common form of dwarfism in man, is a dominant genetic disorder caused by a point mutation (G380R) in the transmembrane region of fibroblast growth factor receptor 3 (FGFR3). We used gene targeting to introduce the human achondroplasia mutation into the murine FGFR3 gene. Heterozygotes for this point mutation that carried the neo cassette were normal whereas neo+ homozygotes had a phenotype similar to FGFR3-deficient mice, exhibiting bone overgrowth. This was because of interference with mRNA processing in the presence of the neo cassette. Removal of the neo selection marker by Cre/loxP recombination yielded a dominant dwarf phenotype. These mice are distinguished by their small size, shortened craniofacial area, hypoplasia of the midface with protruding incisors, distorted brain case with anteriorly shifted foramen magnum, kyphosis, and narrowed and distorted growth plates in the long bones, vertebrae, and ribs. These experiments demonstrate that achondroplasia results from a gain-of FGFR3-function leading to inhibition of chondrocyte proliferation. These achondroplastic dwarf mice represent a reliable and useful model for developing drugs for potential treatment of the human disease.
Scientific Publication
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