Multiple roles for neurofibromin in skeletal development and growth

Mateusz Kolanczyk, Nadine Kossler, Jirko Kühnisch, Liron Lavitas, Sigmar Stricker, Ulrich Wilkening, Inderchand Manjubala, Peter Fratzl, Ralf Spörle, Bernhard G. Herrmann, Luis F. Parada, Uwe Kornak, Stefan Mundlos

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

Neurofibromatosis type 1 (NF1) is a prevalent genetic disorder primarily characterized by the formation of neurofibromas, café-au-lait spots and freckling. Skeletal abnormalities such as short stature or bowing/pseudarthrosis of the tibia are relatively common. To investigate the role of the neurofibromin in skeletal development, we crossed Nf1flox mice with Prx1Cre mice to inactivate Nf1 in undifferentiated mesenchymal cells of the developing limbs. Similar to NF1 affected individuals, Nf1Prx1 mice show bowing of the tibia and diminished growth. Tibial bowing is caused by decreased stability of the cortical bone due to a high degree of porosity, decreased stiffness and reduction in the mineral content as well as hyperosteoidosis. Accordingly, osteoblasts show an increase in proliferation and a decreased ability to differentiate and mineralize in vitro. The reduction in growth is due to lower proliferation rates and a differentiation defect of chondrocytes. Abnormal vascularization of skeletal tissues is likely to contribute to this pathology as it exerts a negative effect on cortical bone stability. Furthermore, Nf1 has an important role in the development of joints, as shown by fusion of the hip joints and other joint abnormalities, which are not observed in neurofibromatosis type I. Thus, neurofibromin has multiple essential roles in skeletal development and growth.

Original languageEnglish (US)
Pages (from-to)874-886
Number of pages13
JournalHuman molecular genetics
Volume16
Issue number8
DOIs
StatePublished - Apr 15 2007

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Multiple roles for neurofibromin in skeletal development and growth'. Together they form a unique fingerprint.

  • Cite this

    Kolanczyk, M., Kossler, N., Kühnisch, J., Lavitas, L., Stricker, S., Wilkening, U., Manjubala, I., Fratzl, P., Spörle, R., Herrmann, B. G., Parada, L. F., Kornak, U., & Mundlos, S. (2007). Multiple roles for neurofibromin in skeletal development and growth. Human molecular genetics, 16(8), 874-886. https://doi.org/10.1093/hmg/ddm032