| First Author | Cryns K | Year | 2008 |
| Journal | Neuropsychopharmacology | Volume | 33 |
| Issue | 3 | Pages | 674-84 |
| PubMed ID | 17460611 | Mgi Jnum | J:157887 |
| Mgi Id | MGI:4437202 | Doi | 10.1038/sj.npp.1301431 |
| Citation | Cryns K, et al. (2008) IMPA1 is essential for embryonic development and lithium-like pilocarpine sensitivity. Neuropsychopharmacology 33(3):674-84 |
| abstractText | Lithium has been the standard pharmacological treatment for bipolar disorder over the last 50 years; however, the molecular targets through which lithium exerts its therapeutic effects are still not defined. We characterized the phenotype of mice with a dysfunctional IMPA1 gene (IMPA1-/-) to study the in vivo physiological functions of IMPA1, in general, and more specifically its potential role as a molecular target in mediating lithium-dependent physiological effects. Homozygote IMPA1-/- mice died in utero between days 9.5 and 10.5 post coitum (p.c.) demonstrating the importance of IMPA1 in early embryonic development. Intriguingly, the embryonic lethality could be reversed by myo-inositol supplementation via the pregnant mothers. In brains of adult IMPA1-/- mice, IMPase activity levels were found to be reduced (up to 65% in hippocampus); however, inositol levels were not found to be altered. Behavioral analysis of the IMPA1-/- mice indicated an increased motor activity in both the open-field test and the forced-swim test as well as a strongly increased sensitivity to pilocarpine-induced seizures, the latter supporting the idea that IMPA1 represents a physiologically relevant target for lithium. In conclusion the IMPA1-/- mouse represents a novel model to study inositol homeostasis, and indicates that genetic inactivation of IMPA1 can mimic some actions of lithium. |
