Lasp1 misexpression influences chondrocyte differentiation in the vertebral column

• Published in: The International journal of developmental biology Vol. 53; no. 7; pp. 983 - 991
• Main Authors: Hermann-Kleiter, Natascha, Ghaffari-Tabrizi, Nassim, Blumer, Michael J F, Schwarzer, Christoph, Mazur, Magdalena A, Artner, Isabella
• Format: Journal Article
• Language: English
• Published: Spain 2009
• Subjects: acid; Animals; Basic Medicine; cartilage bone transition; Cell and Molecular Biology; Cell Differentiation - genetics; Cell- och molekylärbiologi; Chondrocytes - cytology; Chondrocytes - metabolism; Chondrogenesis - genetics; Chondrogenesis - physiology; collagen; Collagen - genetics; Cytoskeletal Proteins; Female; folic acid; Folic Acid - pharmacology; Gene Expression; Homeodomain Proteins - genetics; Homeodomain Proteins - physiology; LIM Domain Proteins; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Mice, Transgenic; Mutagenesis, Insertional; Neoplasm Proteins - genetics; Neoplasm Proteins - physiology; Osteogenesis - genetics; Osteogenesis - physiology; Paired Box Transcription Factors - genetics; Phenotype; Pregnancy; retinoic; Spine - abnormalities; Spine - cytology; Spine - embryology; Spine - metabolism; Tail - abnormalities; Tail - cytology; Tail - embryology; Tail - metabolism; transgene insertion; Tretinoin - pharmacology
• ISSN: 0214-6282; 1696-3547; 1696-3547
• DOI: 10.1387/ijdb.072435nh

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.