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

Ti Lin, Stacey B. Sandusky, Haipeng Xue, Kenneth W. Fishbein, Richard G. Spencer, Mahendra S. Rao, Clair Ann Francomano

Research output: Contribution to journalArticle

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 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.

Original languageEnglish (US)
Pages (from-to)2863-2871
Number of pages9
JournalHuman Molecular Genetics
Volume12
Issue number21
DOIs
StatePublished - Nov 1 2003

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Thanatophoric Dysplasia
Central Nervous System
Nestin
Oligodendroglia
Hindlimb
Transgenic Mice
Cartilage
Spinal Cord
Head
Body Weight
Newborn Infant
Phenotype
Mutation
Brain

ASJC Scopus subject areas

  • Genetics

Cite this

Lin, T., Sandusky, S. B., Xue, H., Fishbein, K. W., Spencer, R. G., Rao, M. S., & Francomano, C. A. (2003). A central nervous system specific mouse model for thanatophoric dysplasia type II. Human Molecular Genetics, 12(21), 2863-2871. https://doi.org/10.1093/hmg/ddg309

A central nervous system specific mouse model for thanatophoric dysplasia type II. / Lin, Ti; Sandusky, Stacey B.; Xue, Haipeng; Fishbein, Kenneth W.; Spencer, Richard G.; Rao, Mahendra S.; Francomano, Clair Ann.

In: Human Molecular Genetics, Vol. 12, No. 21, 01.11.2003, p. 2863-2871.

Research output: Contribution to journalArticle

Lin, T, Sandusky, SB, Xue, H, Fishbein, KW, Spencer, RG, Rao, MS & Francomano, CA 2003, 'A central nervous system specific mouse model for thanatophoric dysplasia type II', Human Molecular Genetics, vol. 12, no. 21, pp. 2863-2871. https://doi.org/10.1093/hmg/ddg309
Lin T, Sandusky SB, Xue H, Fishbein KW, Spencer RG, Rao MS et al. A central nervous system specific mouse model for thanatophoric dysplasia type II. Human Molecular Genetics. 2003 Nov 1;12(21):2863-2871. https://doi.org/10.1093/hmg/ddg309
Lin, Ti ; Sandusky, Stacey B. ; Xue, Haipeng ; Fishbein, Kenneth W. ; Spencer, Richard G. ; Rao, Mahendra S. ; Francomano, Clair Ann. / A central nervous system specific mouse model for thanatophoric dysplasia type II. In: Human Molecular Genetics. 2003 ; Vol. 12, No. 21. pp. 2863-2871.
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