| First Author | Kayyali US | Year | 1997 |
| Journal | J Neurochem | Volume | 68 |
| Issue | 4 | Pages | 1668-78 |
| PubMed ID | 9084440 | Mgi Jnum | J:39103 |
| Mgi Id | MGI:86484 | Doi | 10.1046/j.1471-4159.1997.68041668.x |
| Citation | Kayyali US, et al. (1997) Cytoskeletal changes in the brains of mice lacking calcineurin A alpha. J Neurochem 68(4):1668-78 |
| abstractText | Hyperphosphorylated tau, the major component of the paired helical filaments of Alzheimer's disease, was found to accumulate in the brains of mice in which the calcineurin A alpha gene was disrupted [calcineurin A alpha knockout (CNA alpha -/-)]. The hyperphosphorylation involved several sites on tau, especially the Ser396 and/or Ser404 recognized by the PHF-1 monoclonal antibody. The increase in phosphorylated tau content occurred primarily in the mossy fibers of the CNA alpha -/- hippocampus, which contained the highest level of calcineurin in brains of wild-type mice. The CNA alpha -/- mossy fibers also contained less neurofilament protein than normal, although the overall level of neurofilament phosphorylation was unchanged. In the electron microscope, the mossy fibers of CNA alpha -/- mice exhibited abnormalities in their cytoskeleton and a lower neurofilament/microtubule ratio than those of wild-type animals. These findings indicate that hyperphosphorylated tau can accumulate in vivo as a result of reduced calcineurin activity and is accompanied by cytoskeletal changes that are likely to have functional consequences on the affected neurons. The CNA alpha -/- mice were found in a separate study to have deficits in learning and memory that may result in part from the cytoskeletal changes in the hippocampus. |
