Table 1.
Experimental Models in Which Inositol Status or Metabolism Is Associated with Neural Tube Closure
| Inositol‐related deficits in NTD causation | NTD type | Comments/mechanism | Reference | |
|---|---|---|---|---|
| Inositol deficiency | Cultured mouse or rat embryos | Exencephaly | NTDs in non‐mutant and mutant strains. Higher incidence in ct strain | Cockroft, 1992 |
| PI4P5KIγ null | PIP kinase generates PI(4,5)P2 | Exencephaly |
Disordered actin Cilia defect? |
Wang, 2007 |
| Inpp5e null | PI(4,5)P2 and PI(3,4,5)P2 phosphatase | Exencephaly | Unstable cilia and ciliopathy phenotypes | Jacoby, 2009 |
| Itpk1 hypomorph | Generates IP(1,3,4,5)P4 and IP(1,3,4,6)P4 | Exencephaly &/or spina bifida | Deficit of higher IPs | Wilson, 2009 |
| NTD prevention by inositol in experimental models | ||||
| Curly tail mouse | Embryo culture; Oral; I.P. injection; sub‐cutaneous route | Spina bifida |
Corrects proliferation defect. Requires activity of PKC isoforms. Chiro‐inositol more effective than myo‐inositol |
Greene, 1997; Cogram, 2002; Cogram, 2004 |
| Hyperglycemia | High glucose in embryo culture | Exencephaly | Restores inositol levels. Arachidonic acid signalling? | Baker, 1990; Hashimoto, 1990; |
| Diabetes | Streptozotocin‐induced diabetes | Exencephaly | Restores inositol levels? | Khandelwal, 1998 |
| Folate‐deficient NTDs | Dietary folate deficiency in wild‐type strain (ct genetic background) | Exencephaly | Unknown | Burren, 2010 |