Biomedical subjects

A Amstutz

Publications and source records attributed to A Amstutz.

4 recordsLinked to original sources

PubMed1999

Coordinate action of Wt1 and a modifier gene supports embryonic survival in the oviduct.

The Wt1 gene, originally identified as a tumor suppressor gene associated with Wilms' tumors, encodes a zinc finger containing transcription factor expressed during gonadal and kidney development. Although Wt1 appears to be required for gonadal and kidney development, no reproductive defects were observed in outbred females heterozygous for a targeted mutation in Wt1. In contrast, no litters were obtained from Wt1 +/- females on a strain 129/Sv inbred genetic background. Ovaries were smaller in Wt1 +/- 129/Sv mice and produced fewer ova, but transplanted Wt1 +/- ovaries from 129/Sv females were able to support successful pregnancies. The inability of Wt1 +/- 129/Sv females to produce successful implantations after ovulation and fertilization appeared to be due to the failure of one-cell embryos to undergo mitosis, such that they were lost in the oviduct before reaching the uterus. Approximately 50% of Wt1 +/- females generated from a backcross of Wt1 +/- 129/Sv:C57BI/6 F1 hybrids to 129/Sv were fertile, indicating the presence of a Wt1 modifier gene that affects survival of the preimplantation embryo. Neither levels of WT1 protein nor the ratio of WT1 spice forms were significantly altered in Wt1 +/- reproductive organs, suggesting that this modifier effect acts downstream of WT1. Wt1 is therefore among a small subset of genes required for survival of the pre-implantation embryo, and appears to function non-autonomously.

Animals↗

PubMed1999

Initial differentiation of the metanephric mesenchyme is independent of WT1 and the ureteric bud.

The early development of the metanephric kidney is characterized by the induced differentiation of mesenchymal cells into a stem cell population that undergoes a mesenchymal to epithelial transformation in response to stimuli from the ureteric bud. The Wilms' tumor suppressor gene, Wt1, is required for mesenchymal cells to complete this developmental program. In the absence of WT1, a prospective metanephric mesenchyme appears, but becomes apoptotic, and outgrowth of the ureteric bud from the Wolffian duct does not occur. Therefore, the examination of Wt1 -/- embryos allows the determination of those markers of early metanephric differentiation that do not require the ureteric bud or WT1 for their expression. Here, we demonstrate that several markers, including Pax-2, Six-2, and GDNF, were present as RNAs in the metanephric mesenchyme of Wt1 -/- embryos. These findings demonstrate that the metanephric mesenchyme in mutant embryos has begun to differentiate towards the nephrogenic lineage, and that this early differentiation does not require either WT1 or the presence of the ureteric bud. To determine whether WT1 functions other than to induce expression of factors that stimulate ureteric bud outgrowth, Wt1 -/- metanephric mesenchymes were recombined with wild-type ureteric buds in organ culture, but this failed to rescue tubulogenesis. However, the Wolffian duct from Wt1 -/- embryos was a competent inducer of wild-type metanephric mesenchyme.

Animals↗

PubMed1997

Supramolecular Materials: Self-Organized Nanostructures

Miniaturized triblock copolymers have been found to self-assemble into nanostructures that are highly regular in size and shape. Mushroom-shaped supramolecular structures of about 200 kilodaltons form by crystallization of the chemically identical blocks and self-organize into films containing 100 or more layers stacked in a polar arrangement. The polar supramolecular material exhibits spontaneous second-harmonic generation from infrared to green photons and has an adhesive tape-like character with nonadhesive-hydrophobic and hydrophilic-sticky opposite surfaces. The films also have reasonable shear strength and adhere tenaciously to glass surfaces on one side only. The regular and finite size of the supramolecular units is believed to be mediated by repulsive forces among some of the segments in the triblock molecules. A large diversity of multifunctional materials could be formed from regular supramolecular units weighing hundreds of kilodaltons.

Journal Article↗

PubMed1997

Sodium/proton antiporter in the euryhaline crab Carcinus maenas: molecular cloning, expression and tissue distribution.

Gill epithelial cells of euryhaline crustaceans demonstrate net inward transport of sodium ions, possibly via apical Na+/H+ antiporters, Na+/K+/2Cl- cotransporters or Na+ channels working in series with the basolateral Na(+) + K(+)-ATPase. We have identified and sequenced the cDNA coding for a crustacean Na+/H+ antiporter, starting with mRNA isolated from gills of the euryhaline green shore crab Carcinus maenas. The complete 2595-base-pair cDNA includes an open reading frame coding for a 673-amino-acid protein. A search of GenBank revealed more than 20 high-scoring matches, all Na+/H+ antiporter sequences from mammalian, amphibian, teleost and nematode species. Injection of Xenopus laevis oocytes with cRNA transcribed from the cloned crab sequence substantially enhanced Na(+)-dependent H+ efflux from the oocytes. Analysis of crab tissue antiporter mRNA levels by semi-quantitative reverse transcription-polymerase chain reaction revealed that posterior and anterior gills of Carcinus maenas expressed this antiporter the most strongly, followed in decreasing order by skeletal muscle, hepatopancreas, hypodermis and heart. Hydropathy and transmembrane alpha-helix analysis suggested a 10-helix membrane-spanning topology of the antiporter protein. It is clear from this study that Carcinus maenas gills vigorously transcribe a gene coding for a Na+/H+ antiporter. Whether these gills also express a gene coding for an epithelial Na+ channel or Na+/K+/2Cl- cotransporter remains to be demonstrated.

Amino Acid Sequence↗