| First Author | Hokkanen S | Year | 2012 |
| Journal | Hum Mol Genet | Volume | 21 |
| Issue | 3 | Pages | 473-84 |
| PubMed ID | 22010047 | Mgi Jnum | J:179606 |
| Mgi Id | MGI:5302754 | Doi | 10.1093/hmg/ddr476 |
| Citation | Hokkanen S, et al. (2012) Lack of Pur-alpha alters postnatal brain development and causes megalencephaly. Hum Mol Genet 21(3):473-84 |
| abstractText | Pur-alpha (Puralpha) plays an important role in a variety of cellular processes including transcriptional regulation, cell proliferation and oncogenic transformation. To better understand the role of Puralpha in the developing and mature brain, we generated Puralpha-deficient mice, which we were able to raise to the age of six months. Puralpha(-/-) mice were born with no obvious pathological condition. We obtained convincing evidence that lack of Puralpha prolongs the postnatal proliferation of neuronal precursor cells both in the hippocampus and in the cerebellum, however, without affecting the overall number of postmitotic neurons. Independent of these findings, we observed alterations in the expression and distribution of the dendritic protein MAP2, the translation of which has been proposed previously to be Puralpha-dependent. At the age of 2 weeks, Puralpha(-/-) mice generated a continuous tremor which persisted throughout lifetime. Finally, adult Puralpha(-/-) mice displayed a megalencephaly and histopathological findings including axonal swellings and hyperphosphorylation of neurofilaments. Our studies underline the importance of Puralpha in the proliferation of neuronal precursor cells during postnatal brain development and suggest a role for Puralpha in the regulation of the expression and cellular distribution of dendritic and axonal proteins. Since recent studies implicate a link between Puralpha and the fragile X tremor/ataxia syndrome, our Puralpha(-/-) mouse model will provide new opportunities for understanding the mechanisms of neurodegeneration. |
