Targeted insertion of two Mthfr promoters in mice reveals temporal- and tissue-specific regulation.

Methylenetetrahydrofolate reductase (MTHFR), a key enzyme in folate metabolism, synthesizes 5-methyltetrahydrofolate, the main circulatory form of folate which is required for maintaining nontoxic levels of homocysteine and providing one-carbon units for methylation. A common 677C → T variant in MTHFR confers mild MTHFR deficiency and has been associated with a number of human disorders, including neural tube defects and vascular disease. Two promoters of Mthfr, designated as upstream and downstream promoters, are located upstream of a transcription start site cluster and have previously demonstrated cell-specific activities.

High intake of folic acid disrupts embryonic development in mice.

Background: Folic acid fortification and supplementation has increased folate intake and blood folate concentrations and successfully reduced the incidence of neural tube defects. However, the developmental consequences of high folate intake are unknown. This study investigated the impact of high folate intake, alone or with methylenetetrahydrofolate reductase (MTHFR) deficiency, on embryonic and placental development in mice.

Methylenetetrahydrofolate reductase deficiency and low dietary folate increase embryonic delay and placental abnormalities in mice.

Background: Despite extensive research on mild methylenetetrahydrofolate reductase (MTHFR) deficiency and low dietary folate in different disorders, the association of these metabolic disturbances with a variety of congenital defects and pregnancy complications remains controversial. In this study we investigated the effects of MTHFR and dietary folate deficiency at 10.5 days post coitum (dpc) in our mouse model of mild MTHFR deficiency.

Bovine SNRPN methylation imprint in oocytes and day 17 in vitro-produced and somatic cell nuclear transfer embryos.

Findings from recent studies have suggested that the low survival rate of animals derived via somatic cell nuclear transfer (SCNT) may be in part due to epigenetic abnormalities brought about by this procedure. DNA methylation is an epigenetic modification of DNA that is implicated in the regulation of imprinted genes. Genes subject to genomic imprinting are expressed monoallelically in a parent of origin-dependent manner and are important for embryo growth, placental function, and neurobehavioral processes.

Postnatal cerebellar defects in mice deficient in methylenetetrahydrofolate reductase.

Patients with severe deficiency of methylenetetrahydrofolate reductase (MTHFR) suffer from a wide variety of neurological problems, which can begin in the neonatal period. MTHFR is a critical enzyme in folate metabolism; the product of the MTHFR reaction, 5-methyltetrahydrofolate, is required for homocysteine remethylation to methionine and synthesis of S-adenosylmethionine (SAM). To understand the mechanisms by which MTHFR deficiency leads to significant neuropathology, we examined early postnatal brain development in mice with a homozygous knockout of the Mthfr gene.

Mechanism of biotin responsiveness in biotin-responsive multiple carboxylase deficiency.

Holocarboxylase synthetase (HCS) catalyses the biotinylation of the four biotin-dependent carboxylases found in humans. A deficiency in HCS results in biotin-responsive multiple carboxylase deficiency. We have evaluated the biotin responsiveness associated with six missense mutations previously identified in affected patients by expression of plasmids containing the mutated HCS in an Escherichia coli strain mutated in the corresponding BirA gene.

Rehearsal strategies and recall performance in boys with and without attention deficit hyperactivity disorder.

Examined differences in recall performance and rehearsal strategies in boys with Attention Deficit Hyperactivity Disorder (ADHD) and comparison boys using an overt rehearsal procedure on a self-paced, multitrial, free recall task. Boys with ADHD recalled fewer words, tended to spend less time rehearsing the items, and spent less time attempting to retrieve them. Although they did not rehearse items less frequently than comparison boys, they relied almost exclusively on repetition of single items.