title: A central nervous system specific mouse model for thanatophoric dysplasia type II.
abstract: 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.
authors.affiliation: Laboratory of Genetics, National Institute on Aging, Baltimore Maryland, 21224-6814, USA.
authors.forename: Ti
authors.initials: T
authors.lastname: Lin
authors.forename: Stacey B
authors.initials: SB
authors.lastname: Sandusky
authors.forename: Haipeng
authors.initials: H
authors.lastname: Xue
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Fishbein
authors.forename: Richard G
authors.initials: RG
authors.lastname: Spencer
authors.forename: Mahendra S
authors.initials: MS
authors.lastname: Rao
authors.forename: Clair A
authors.initials: CA
authors.lastname: Francomano
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D003713:Dendritic Cells / Q000473:pathology; D005314:Embryonic and Fetal Development; D006801:Humans; D019426:Integrases / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics* / Q000378:metabolism; D013116:Spinal Cord / Q000196:embryology / Q000378:metabolism / Q000473:pathology*; D013796:Thanatophoric Dysplasia / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D017468:Receptors, Fibroblast Growth Factor; D014764:Viral Proteins; C496365:FGFR3 protein, human; C496366:Fgfr3 protein, mouse; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3; C045073:Cre recombinase; D019426:Integrases