| First Author | Stankewich MC | Year | 2011 |
| Journal | J Cell Sci | Volume | 124 |
| Issue | Pt 23 | Pages | 3956-66 |
| PubMed ID | 22159418 | Mgi Jnum | J:186305 |
| Mgi Id | MGI:5431891 | Doi | 10.1242/jcs.080374 |
| Citation | Stankewich MC, et al. (2011) Cell organization, growth, and neural and cardiac development require alphaII-spectrin. J Cell Sci 124(Pt 23):3956-66 |
| abstractText | Spectrin alpha2 (alphaII-spectrin) is a scaffolding protein encoded by the Spna2 gene and constitutively expressed in most tissues. Exon trapping of Spna2 in C57BL/6 mice allowed targeted disruption of alphaII-spectrin. Heterozygous animals displayed no phenotype by 2 years of age. Homozygous deletion of Spna2 was embryonic lethal at embryonic day 12.5 to 16.5 with retarded intrauterine growth, and craniofacial, neural tube and cardiac anomalies. The loss of alphaII-spectrin did not alter the levels of alphaI- or betaI-spectrin, or the transcriptional levels of any beta-spectrin or any ankyrin, but secondarily reduced by about 80% the steady state protein levels of betaII- and betaIII-spectrin. Residual betaII- and betaIII-spectrin and ankyrins B and G were concentrated at the apical membrane of bronchial and renal epithelial cells, without impacting cell morphology. Neuroepithelial cells in the developing brain were more concentrated and more proliferative in the ventricular zone than normal; axon formation was also impaired. Embryonic fibroblasts cultured on fibronectin from E14.5 (Spna2(-/-)) animals displayed impaired growth and spreading, a spiky morphology, and sparse lamellipodia without cortical actin. These data indicate that the spectrin-ankyrin scaffold is crucial in vertebrates for cell spreading, tissue patterning and organ development, particularly in the developing brain and heart, but is not required for cell viability. |
