| First Author | Kim YS | Year | 2010 |
| Journal | Cerebellum | Volume | 9 |
| Issue | 3 | Pages | 310-23 |
| PubMed ID | 20393820 | Mgi Jnum | J:175342 |
| Mgi Id | MGI:5285161 | Doi | 10.1007/s12311-010-0163-z |
| Citation | Kim YS, et al. (2010) Altered cerebellar development in nuclear receptor TAK1/ TR4 null mice is associated with deficits in GLAST(+) glia, alterations in social behavior, motor learning, startle reactivity, and microglia. Cerebellum 9(3):310-23 |
| abstractText | Previously, deficiency in the expression of the nuclear orphan receptor TAK1 was found to be associated with delayed cerebellar granule cell migration and Purkinje cell maturation with a permanent deficit in foliation of lobules VI-VII, suggesting a role for TAK1 in cerebellum development. In this study, we confirm that TAK1-deficient (TAK1(-/-)) mice have a smaller cerebellum and exhibit a disruption of lobules VI-VII. We extended these studies and show that at postnatal day 7, TAK1(-/-) mice exhibit a delay in monolayer maturation of dysmorphic calbindin 28K-positive Purkinje cells. The astrocyte-specific glutamate transporter (GLAST) was expressed within Bergmann fibers and internal granule cell layer at significantly lower levels in the cerebellum of TAK1(-/-) mice. At PND21, Golgi-positive Purkinje cells in TAK1(-/-) mice displayed a smaller soma (18%) and shorter distance to first branch point (35%). Neuronal death was not observed in TAK1(-/-) mice at PND21; however, activated microglia were present in the cerebellum, suggestive of earlier cell death. These structural deficits in the cerebellum were not sufficient to alter motor strength, coordination, or activity levels; however, deficits in acoustic startle response, prepulse startle inhibition, and social interactions were observed. Reactions to a novel environment were inhibited in a light/dark chamber, open-field, and home-cage running wheel. TAK1(-/-) mice displayed a plateau in performance on the running wheel, suggesting a deficit in learning to coordinate performance on a motor task. These data indicate that TAK1 is an important transcriptional modulator of cerebellar development and neurodevelopmentally regulated behavior. |
