Developmental control of inositol phosphate biosynthesis is altered in the brain of both curly and phenotypically normal straight tail mutant mice.
BACKGROUND
Altered levels of inositol phosphate in the central nervous system (CNS) are hypothesized to produce distorted brain signaling and lead to numerous neurologic maladies. Little is known of mechanisms controlling the complex metabolic flux of inositol phosphate. Less is known of controls that regulate inositol-phosphate biosynthesis in the mammalian brain. The expression of 1L-myo-inositol-1 phosphate synthase (MIP), the only enzyme known to synthesize inositol phosphate, was studied in the brain of normal (CBA) and curly tail (CT) mutant mice. The CT strain exhibits a neural tube defect, spina bifida, responsive to inositol supplementation, but not to folic acid treatment.


METHODS
Utilizing enzyme assays to determine the specific activity of MIP, Western blotting to detect expression, gas chromatography/mass spectrometry to measure inositol concentration, and statistical analyses to evaluate quantitative data, MIP expression was analyzed in newborn, young, and adult brains of CBA and CT (curly tail [ct-CT] and straight tail [st-CT]) mutant mice.


RESULTS
Data analyses suggest there is a significant difference in MIP activity in the brain of CBA mice as compared to that of CT mutant mice and that temporal and spatial control of MIP expression and inositol concentrations are altered in the brain of both the ct-CT and phenotypically normal st-CT mutant. Moreover, two differentially expressed forms of MIP were identified in the adult mouse brain.


CONCLUSIONS
These findings implicate a role for MIP in the maturation of the CNS and evoke a hypothesis regarding the regulation of inositol phosphate biosynthesis in brain development.
Alebous
Hana Dawood Ali
HD
Department of Biology, Jordan University, Amman, Jordan.
Cartee
Robert
R
Vaccari
David
D
Wright
Oneil A
OA
Ahmed
Altan
A
Hood
Ronald D
RD
Johnson
Margaret Dean
MD
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology / Q000254:growth & development* / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000096:biosynthesis*; D051379:Mice; D008808:Mice, Inbred CBA; D008817:Mice, Mutant Strains; D007296:Myo-Inositol-1-Phosphate Synthase / Q000378:metabolism; D010641:Phenotype; D013045:Species Specificity
D007295:Inositol Phosphates; D007294:Inositol; D007296:Myo-Inositol-1-Phosphate Synthase