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 tall 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.
ASJC Scopus subject areas
- Molecular Biology