A central nervous system specific mouse model for thanatophoric dysplasia type II

To investigate the specific effect of the Fgfr3 K644E mutation on central nervous system (CNS) development, we have generated tissue-specific TDII mice by crossing Fgfr3+/K644E-neo transgenic mice with CNS-specific Nestin-cre or cartilage-specific Col2a1-cre mice. TDII/Nestin-cre (TDII-N) neonates d...

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Bibliographic Details
Published in:	Human molecular genetics Vol. 12; no. 21; pp. 2863 - 2871
Main Authors:	Lin, Ti, Sandusky, Stacey B., Xue, Haipeng, Fishbein, Kenneth W., Spencer, Richard G., Rao, Mahendra S., Francomano, Clair A.
Format:	Journal Article
Language:	English
Published:	Oxford Oxford University Press 01-11-2003 Oxford Publishing Limited (England)
Subjects:	Amino Acid Substitution Animals Biological and medical sciences Brain - embryology Brain - metabolism Brain - pathology Cell Differentiation - genetics Cell Division - genetics Classical genetics, quantitative genetics, hybrids Dendritic Cells - pathology Embryonic and Fetal Development Fundamental and applied biological sciences. Psychology Genetics of eukaryotes. Biological and molecular evolution Human Humans Integrases - metabolism Magnetic Resonance Imaging Mice Mice, Transgenic Molecular and cellular biology Phenotype Protein-Tyrosine Kinases - genetics Protein-Tyrosine Kinases - metabolism Receptor, Fibroblast Growth Factor, Type 3 Receptors, Fibroblast Growth Factor - genetics Receptors, Fibroblast Growth Factor - metabolism Spinal Cord - embryology Spinal Cord - metabolism Spinal Cord - pathology Thanatophoric Dysplasia - genetics Thanatophoric Dysplasia - metabolism Viral Proteins - metabolism Animal model Vertebrata Dysplasia Mammalia Mouse Rodentia Central nervous system Genetics
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Summary:	To investigate the specific effect of the Fgfr3 K644E mutation on central nervous system (CNS) development, we have generated tissue-specific TDII mice by crossing Fgfr3+/K644E-neo transgenic mice with CNS-specific Nestin-cre or cartilage-specific Col2a1-cre mice. TDII/Nestin-cre (TDII-N) neonates did not demonstrate a profound skeletal phenotype. TDII-N pups were comparable to their wild-type littermates in terms of tail length, fore and hindlimbs, and body weight; however, many pups exhibited notably round heads. MRI and histochemical analysis illustrated asymmetric changes in cortical thickness and cerebellar abnormalities in TDII-N mice, which correlate with brain abnormalities observed in human TDII patients. Such abnormalities were not seen in TDII/Col2a1-cre (TDII-C) mice. Upon examination of adult TDII-N spinal cord, premature differentiation of oligodendrocyte progenitors was observed. Overall, these data indicate that the tissue-specific mouse model is an excellent system for studying the role of Fgfr3 in the developing CNS.
Bibliography:	local:ddg309 istex:9ED1C6B30BDEC89A053BE5B674172673CC671209 ark:/67375/HXZ-LVKZPRL8-0 ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0964-6906 1460-2083 1460-2083
DOI:	10.1093/hmg/ddg309