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 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.
Lin
Ti
T
Laboratory of Genetics, National Institute on Aging, Baltimore Maryland, 21224-6814, USA.
Sandusky
Stacey B
SB
Xue
Haipeng
H
Fishbein
Kenneth W
KW
Spencer
Richard G
RG
Rao
Mahendra S
MS
Francomano
Clair A
CA
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
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