| First Author | B?hm D | Year | 2002 |
| Journal | Mol Cell Neurosci | Volume | 21 |
| Issue | 4 | Pages | 584-601 |
| PubMed ID | 12504592 | Mgi Jnum | J:81244 |
| Mgi Id | MGI:2448431 | Doi | 10.1006/mcne.2002.1199 |
| Citation | Bohm D, et al. (2002) Disruption of PLC-beta1-Mediated Signal Transduction in Mutant Mice Causes Age-Dependent Hippocampal Mossy Fiber Sprouting and Neurodegeneration. Mol Cell Neurosci 21(4):584-601 |
| abstractText | Aberrant reorganization of hippocampal mossy fibers occurs in human temporal lobe epilepsy and rodent epilepsy models. We generated a mouse model showing massive late-onset aberrant mossy fiber sprouting in the adult hippocampus. The mutation in this mouse model derives from an intronic insertion of transgene DNA in the mouse PLC-beta1 gene (PLC-beta1(-/-)(TC) mutation) leading to a splice mutation of the PLC-beta1 gene and a complete loss of downstream PLC-beta1 expression. PLC-beta1(-/-)(TC) mutants develop a loss of NMDA-receptors in the stratum oriens of region CA1, apoptotic neuronal death, and reduced hippocampal PKC activity. The phenotype of these mice further consists of a late-onset epileptiform hyperexcitability, behavioral modifications in a radial maze and in an open field, female nurturing defect, and male infertility. In the present study, we provide evidence that the arising of the behavioral phenotype in PLC-beta1(-/-)(TC) mice correlates in time with the development of the aberrant mossy fiber projections and that the disruption of the PLC-beta1-mediated signal transduction pathway may lead to a functional cholinergic denervation, which could cause hippocampal remodeling and, in consequence, epileptiform hyperexcitability. |
