Int. J. Dev. Biol. - Lasp1 misexpression influences chondrocyte differentiation in the vertebral column

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   Int. J. Dev. Biol. 53: 983 - 991 (2009)
   doi: 10.1387/ijdb.072435nh

   © UBC Press

Lasp1 misexpression influences chondrocyte differentiation in the vertebral column

Natascha Hermann-Kleiter*^,1, Nassim Ghaffari-Tabrizi², Michael J.F. Blumer³, Christoph Schwarzer⁴, Magdalena A. Mazur⁵ and Isabella Artner*^,5

¹Dept. Medical Genetics, Molecular and Clinical Pharmacology Medical University, Innsbruck, Austria, ² Institute of Pathophysiology and Immunology, Centre of Molecular Medicine, Medical University of Graz, Austria, ³Dept. Anatomy, Histology and Embryology, Division of Clinical and Functional Anatomy, Innsbruck Medical University, Innsbruck, Austria, ⁴Dept. Pharmacology, Innsbruck Medical University, Innsbruck, Austria and ⁵Developmental Biology Program, Stem Cell Center, Lund University, Sweden

ABSTRACT The mouse mutant wavy tail Tg(Col1a1-lacZ)304ng was created through transgene insertion and exhibits defects of the vertebral column. Homozygous mutant animals have compressed tail vertebrae and wedge-shaped intervertebral discs, resulting in a meandering tail. Delayed closure of lumbar neural arches and lack of processus spinosi have been observed; these defects become most prominent during the transition from cartilage to bone. The spina bifida was resistant to folic acid treatment, while retinoic acid administration caused severe skeletal defects in the mutant, but none in wild type control animals. The transgene integrated at chromosome 11 band D, in an area of high gene density. The insertion site was located between the transcription start sites of the Rpl23 and Lasp1 genes. LASP1 (an actin binding protein involved in cell migration and survival) was found to be produced in resting and hypertrophic chondrocytes in the vertebrae. In mutant vertebrae, temporal and spatial misexpression of Lasp1 was observed, indicating that alterations in Lasp1 transcription are most likely responsible for the observed phenotype. These data reveal a yet unappreciated role of Lasp1 in chondrocyte differentiation during cartilage to bone transition.

Key words: transgene insertion, cartilage bone transition, folic acid, retinoic acid, collagen

*Corresponding author e-mail: natascha.kleiter@i-med.ac.at; isabella.artner@med.lu.se