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.

Maternal folate deficiency affects proliferation, but not apoptosis, in embryonic mouse heart.

Low dietary folate and deficiency of methylenetetrahydrofolate reductase (Mthfr) were reported to increase the risk for congenital heart defects, but contributory mechanisms have not been elucidated. Because low folate and absent MTHFR activity were shown to affect proliferation and apoptosis in developing neural tissue, we examined these processes in the myocardium of embryos from Mthfr +/+ and Mthfr +/- mice fed control diets (CD) or folic acid-deficient diets (FADD). Mice consumed the designated diets for 8 wk, from weaning and through pregnancy until they were killed.

Neuronal apoptosis inhibitory protein is expressed in developing kidney and is regulated by PAX2.

During fetal kidney development, the extent of ureteric bud (UB) branching will determine final nephron endowment for life. Nephron number varies widely among normal humans and those who are born at the low end of the nephron number spectrum may be at risk for essential hypertension in adulthood. Little is known about how nephron number is set.

Dynamic expression of DNMT3a and DNMT3b isoforms during male germ cell development in the mouse.

In the male germ line, sequence-specific methylation patterns are initially acquired prenatally in diploid gonocytes and are further consolidated after birth during spermatogenesis. It is still unclear how DNA methyltransferases are involved in establishing and/or maintaining these patterns in germ cells, or how their activity is regulated. We compared the temporal expression patterns of the postulated de novo DNA methyltransferases DNMT3a and DNMT3b in murine male germ cells.

Suppression of ureteric bud apoptosis rescues nephron endowment and adult renal function in Pax2 mutant mice.

The molecular mechanisms that set congenital nephron number are unknown. However, humans with modest suboptimal nephron number may be at increased risk for essential hypertension, and those with more severe nephron deficits at birth may develop progressive renal insufficiency. A model of branching morphogenesis during fetal kidney development in which the extent of ureteric bud arborization is dependent on suppression of programmed cell death has been proposed.

Long-term recurrent hypoxia in developing rat attenuates respiratory responses to subsequent acute hypoxia.

Whereas definitive treatment of pediatric conditions associated with hypoxemia reverses many pathologic symptoms, some physiologic dysfunctions appear to persist. These abnormalities are attributed to long-lasting central effects of prior hypoxia. To investigate such effects in an animal model, male rats were exposed to FiO2 = 0.

Structural and functional consequences of trolox C treatment in the rat model of postnatal hyperoxia.

Purpose: Previous studies have shown that newborn rats exposed to hyperoxia within the first 2 weeks of life develop vasculopathy in addition to permanent changes in retinal structure and function. It has also been suggested that free radicals may be the source of these pathologic effects. Trolox C, a water-soluble analogue of vitamin E, was previously shown to limit the vascular consequences of exposure to postnatal hyperoxia.

Lgl1 is suppressed in oxygen toxicity animal models of bronchopulmonary dysplasia and normalizes during recovery in air.

Bronchopulmonary dysplasia (BPD), a major cause of morbidity in premature infants, is characterized by arrest of lung growth and inhibited alveologenesis. We had earlier cloned late-gestation lung 1 (LGL1), a glucocorticoid (GC)-induced, developmentally regulated gene in lung mesenchyme, and showed that reduced levels of late-gestation lung 1 protein (lgl1) inhibit lung branching. Maximal fetal expression of LGL1 is concordant with the onset of alveolar septation, suggesting an additional role for lgl1 in alveologenesis.

Gamete imprinting: setting epigenetic patterns for the next generation.

The acquisition of genomic DNA methylation patterns, including those important for development, begins in the germ line. In particular, imprinted genes are differentially marked in the developing male and female germ cells to ensure parent-of-origin-specific expression in the offspring. Abnormalities in imprints are associated with perturbations in growth, placental function, neurobehavioural processes and carcinogenesis.

Impact of methylenetetrahydrofolate reductase deficiency and low dietary folate on the development of neural tube defects in splotch mice.

Background: The etiology of neural tube defects (NTDs) is multifactorial, with environmental and genetic determinants. Folate supplementation prevents the majority of NTDs, and a polymorphism in methylenetetrahydrofolate reductase (MTHFR) has become recognized as a genetic risk factor. The mechanisms by which folate affects NTD development are unclear.

RPGRIP1 is mutated in Leber congenital amaurosis: a mini-review.

RPGRIP1 encodes the retinitis pigmentosa GTPase interacting protein 1 and interacts with RPGR, the latter represents the major X-linked RP (XRRP) gene, as it accounts for 70-80% of the XRRP patients and up to 13% of all RP patients. RPGRIP1 contains a C-terminal RPGR interacting domain (RID) and a coiled-coil (CC) domain, which is homologous to proteins involved in vesicular trafficking. The interactions between the two proteins is between the RCC1-homologous domain of RPGR (RHD) and the RPGR-interacting domain of RPGRIP1 (RID).

The photopic ERG of the albino guinea pig (Cavia porcellus): a model of the human photopic ERG.

Altricial rodents such as rats and mice are probably the most widely used animal model in the electroretinogram (ERG) literature. However, while the scotopic responses of these rodents share obvious similarities with that of humans, their photopic electroretinograms are strikingly different. For instance, the photopic ERGs of rats and mice include, when measurable, a minimal a-wave, while the b-wave is of much larger amplitude than that of humans.

Phenylalanine ammonia lyase, enzyme substitution therapy for phenylketonuria, where are we now?

Phenylketonuria (PKU) is an autosomal recessive genetic disorder in which mutations in the phenylalanine-4-hydroxylase (PAH) gene result in an inactive enzyme (PAH, EC 1.14.16.

Interleukin-13-dependent bronchial hyper-responsiveness following isolated upper-airway allergen challenge in a murine model of allergic rhinitis and asthma.

Background: We have previously shown that isolated allergic sensitization and challenge of the upper airway results in lower-airway inflammation, which supports the concept of the united airways.

Objective: This study investigates the hypothesis that isolated upper-airway allergic sensitization is sufficient to induce bronchial hyper-responsiveness (BHR), characteristic of asthma, and that IL-13 is an essential mediator in both the upper and lower airways.

Methods: BALB/c mice were sensitized and challenged by intranasal instillation of allergen ovalbumin (OVA) using our standard protocol.

Ontogeny of respiratory sensitivity and tolerance to the mu-opioid agonist fentanyl in rat.

Whereas developmental changes in analgesic sensitivity and tolerance to the mu-opioid agonist fentanyl have been reported, knowledge of respiratory responses to that drug is lacking. Using 7- and 14-day-old (P7, P14) and adult conscious rats, we first established, using whole body plethysmography, the fentanyl dose that decreased minute ventilation by 50% (ED50) at each age. ED50 increased with postnatal age (40, 60 and 120 microg/kg sc, respectively), indicating a high sensitivity to fentanyl in the youngest rats that decreased with maturation.

Regulation of phosphorus homeostasis by the type iia na/phosphate cotransporter.

The type IIa Na/phosphate (Pi) cotransporter (Npt2a) is expressed in the brush border membrane (BBM) of renal proximal tubular cells where the bulk of filtered Pi is reabsorbed. Disruption of the Npt2a gene in mice elicits hypophosphatemia, renal Pi wasting, and an 80% decrease in renal BBM Na/Pi cotransport, and led to the demonstration that Npt2a is the target for hormonal and dietary regulation of renal Pi reabsorption. Regulation is achieved by changes in BBM abundance of Npt2a protein and requires the interaction of Npt2a with various scaffolding and regulatory proteins.

Maternal methylenetetrahydrofolate reductase deficiency and low dietary folate lead to adverse reproductive outcomes and congenital heart defects in mice.

Background: Genetic or nutritional disturbances in folate metabolism may affect embryonic development because of the critical role of folate in nucleotide synthesis and methylation reactions. The possible role of a mild deficiency in methylenetetrahydrofolate reductase (MTHFR) and low dietary folate in pregnancy outcomes and heart morphogenesis requires further investigation.

Objective: We investigated the effect of mild MTHFR deficiency, low dietary folate, or both on resorption rates, on length and weight, and on the incidence of heart malformations in murine embryos.

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.

Platelet-activating factor antagonists decrease follicular dendritic-cell stimulation of human B lymphocytes.

Both B-lymphoblastoid cell lines and tonsillar B lymphocytes express receptors for platelet-activating factor (PAF). In lymph node germinal centres, B lymphocytes interact with follicular dendritic cells (FDCs), which present antigen-containing immune complexes to B lymphocytes. FDCs have phenotypic features that are similar to those of stromal cells and monocytes and may therefore be a source of lipid mediators.

Modulation of the human photopic ERG luminance-response function with the use of chromatic stimuli.

In response to progressively brighter flashes, the amplitude of the photopic b-wave of the human electroretinogram (ERG) first increases, then saturates at a maximal value (V(max)) to finally decrease with the brightest flashes. The purpose of this study was to investigate if this "photopic hill" could be modulated with the use of stimuli of different wavelengths. ERGs were evoked to flashes of white, blue, green and red light presented against a white background in 30 normal subjects.

Prolonged and unsoothable crying bouts in infants with and without colic.

ABSTRACT.: The authors sought to determine which features of early distress were "excessive" and specific to the first months of life as described by diary recordings. In a short-term, longitudinal, controlled study, total daily amount, frequency, and bout duration of fussing, crying, and unsoothable crying were derived from validated diaries kept by parents of infants with and without diary-defined colic at 6 weeks and 5 months recruited from primary pediatrics practices.

Accumulation of methotrexate and methotrexate polyglutamates in lymphoblasts and treatment outcome in children with B-progenitor-cell acute lymphoblastic leukemia: a Pediatric Oncology Group study.

We reported that children with B-progenitor-cell acute lymphoblastic leukemia (BpALL) treated in the early 1980s whose lymphoblasts accumulated high levels of methotrexate (MTX) and of methotrexate polyglutamates (MTXPGs) in vitro had an improved 5-year event-free survival (EFS) (65% (standard error (s.e.) 12%) vs 22% (s.

Infertility in 5,10-methylenetetrahydrofolate reductase (MTHFR)-deficient male mice is partially alleviated by lifetime dietary betaine supplementation.

Metabolism of folate is essential for proper cellular function. Within the folate pathway, methylenetetrahydrofolate reductase (MTHFR) reduces 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a methyl donor for remethylation of homocysteine to methionine, the precursor of S-adenosylmethionine. S-adenosylmethionine is the methyl donor for numerous cellular reactions.

A three base pair deletion encoding the amino acid (lysine-270) in the alpha-cone transducin gene.

Purpose: Cone transducin plays an important role in interacting with the cone photoreceptor visual pigments and activating the cGMP-dependent phosphodiesterase. The human gene for the alpha-subunit of cone transducin (GNAT2) has been cloned and characterized. Recently achromatopsia has been associated with mutations in this gene.