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The neonatal brain mitochondrial ribosomal protein subunit 6 gene expression is normal in the lethal Smit1 knockout and independent of the rescue of the phenotype with prenatal myo‐inositol treatment
Author(s) -
Buccafusca Roberto,
Venditti Charles,
Kenyon Lawrence,
Johanson Roy A,
Golden Jeffrey A,
Coady Michael J,
Berry Gerard T
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.805.13
Subject(s) - biology , inositol , knockout mouse , fetus , gene expression , exon , immunostaining , protein subunit , ribosomal protein , extracellular , gene , endocrinology , medicine , microbiology and biotechnology , receptor , biochemistry , genetics , immunohistochemistry , pregnancy , rna , immunology , ribosome
Myo‐inositol (Ins) is an essential component of phosphatidylinositol, polyphosphoinositides, and inositol polyphosphates including the second messenger, Ins‐1,4,5‐P3. Ins also serves as an organic osmolyte. Active transport of Ins from the extracellular environment is primarily dependent on the sodium/myo‐inositol cotransporter 1, SLC5A3 (SMIT1). To gain insight into the biological role of Ins, and of the SLC5A3 protein, we have generated a knock out mouse model. The Slc5a3 KO newborn mice die post partum, but can be rescued if the pregnant mother is treated with 1% Ins enriched water. Our results show that Ins levels increased in brain and whole KO fetuses following rescue with 1% Ins. Yet, the tissue PtdIns content was normal in the KO with or without Ins treatment. Most importantly, the expression of the mitochondrial ribosomal protein subunit 6 (Mrps6) gene, which shares exon 1 with the Slc5a3 gene, was also not aberrantly expressed in E18.5 KO fetal brain. With or without 1% Ins treatment, selective neuronal immunostaining was normal in the central and peripheral nervous system of E18.5 fetuses and in adult mice, who also had a normal complete necropsy. We conclude that the role of Ins in pathophysiology, and perhaps also in regulation of the SLc5a3/Mrps6 gene(s), which phylogenetically share genomic space since the appearance of vertebrates, requires better delineation, especially in fetal development.