Lasp1 misexpression influences chondrocyte differentiation in the vertebral column.
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.
Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University, Innsbruck, Austria. natascha.kleiter@i-med.ac.at
Natascha
N
Hermann-Kleiter
Nassim
N
Ghaffari-Tabrizi
Michael J F
MJ
Blumer
Christoph
C
Schwarzer
Magdalena A
MA
Mazur
Isabella
I
Artner
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism*; D020219:Chondrogenesis / Q000235:genetics* / Q000502:physiology; D003094:Collagen / Q000235:genetics; D003598:Cytoskeletal Proteins; D005260:Female; D005492:Folic Acid / Q000494:pharmacology; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology; D060588:LIM Domain Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D016254:Mutagenesis, Insertional; D009363:Neoplasm Proteins / Q000235:genetics* / Q000502:physiology; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology; D051761:Paired Box Transcription Factors / Q000235:genetics; D010641:Phenotype; D011247:Pregnancy; D013131:Spine / Q000002:abnormalities / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D013623:Tail / Q000002:abnormalities / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology
D003598:Cytoskeletal Proteins; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; C490692:Lasp1 protein, mouse; D009363:Neoplasm Proteins; D051761:Paired Box Transcription Factors; C070835:PAX1 transcription factor; D014212:Tretinoin; D003094:Collagen; D005492:Folic Acid