Microarray analysis of brain RNA in mice with methylenetetrahydrofolate reductase deficiency and hyperhomocysteinemia.
Methylenetetrahydrofolate reductase (MTHFR) deficiency is the most common genetic cause of hyperhomocysteinemia, which is associated with increased risk for cardiovascular disease, stroke and possibly other neurological disorders. Microarray analysis of brain RNA from day 14 Mthfr(-/-) mice revealed several genes with altered expression. Expression changes in inositol 1,4,5-triphosphate receptor, type 1 (Itpr1), proteolipid protein (Plp), neurogenic differentiation factor 1 (Neurod1), S100 calcium binding protein A8 (S100a8), and methylenetetrahydrofolate dehydrogenase (NAD+ dependent), methenyltetrahydrofolate cyclohydrolase (Mthfd2) were confirmed by RT-PCR. We propose that neuronal damage by hyperhomocysteinemia may involve disruption of intracellular calcium.
Chen
Zhoutao
Z
Department of Biology, McGill University, Montreal, Canada.
Ge
Bing
B
Hudson
Thomas J
TJ
Rozen
Rima
R
D000199:Actins / Q000378:metabolism; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000096:biosynthesis; D040501:Calgranulin A / Q000096:biosynthesis; D020224:Expressed Sequence Tags; D006579:Heterozygote; D020138:Hyperhomocysteinemia / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D045064:Methenyltetrahydrofolate Cyclohydrolase / Q000096:biosynthesis; D008745:Methylation; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000096:biosynthesis; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018991:Myelin Proteolipid Protein / Q000096:biosynthesis; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009474:Neurons / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014157:Transcription Factors / Q000096:biosynthesis
D000199:Actins; D051792:Basic Helix-Loop-Helix Proteins; D002118:Calcium; D015220:Calcium Channels; D040501:Calgranulin A; D053496:Inositol 1,4,5-Trisphosphate Receptors; D045064:Methenyltetrahydrofolate Cyclohydrolase; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP); D042965:Methylenetetrahydrofolate Reductase (NADPH2); D018991:Myelin Proteolipid Protein; D009419:Nerve Tissue Proteins; D012313:RNA; D018160:Receptors, Cytoplasmic and Nuclear; D016194:Receptors, N-Methyl-D-Aspartate; D014157:Transcription Factors; C486336:Neurog1 protein, mouse