Biomedical subjects

D R Beier

Publications and source records attributed to D R Beier.

77 records · Page 5Linked to original sources

PubMed1989

Perinatal lethality (ple): a mutation caused by integration of a transgene into distal mouse chromosome 15.

We have used cytogenetic and recombinational analysis to determine the position of a transgene integrated into the mouse genome. The transgene maps to band F on the physical map of mouse chromosome 15 by in situ analysis and is tightly linked genetically to a cluster of loci that include the mutations caracul (Ca) and microcytic anemia (mk). Genetic analysis of the offspring of noninbred animals carrying the transgene and marker loci demonstrates a significant deficiency of homozygous progeny at weaning. When inbred mice heterozygous for the transgene are mated, about one-quarter of their offspring are homozygous; none of these animals survives more than 1 day after birth. It appears likely that a recessive insertional mutation has occurred as a result of transgene integration into a locus required for postnatal viability. We call this mutation transgenic perinatal lethality (Tg.ple).

Animals↗

PubMed1988

Generation of murine stromal cell lines supporting hematopoietic stem cell proliferation by use of recombinant retrovirus vectors encoding simian virus 40 large T antigen.

The bone marrow is a complex microenvironment made up of multiple cell types which appears to play an important role in the maintenance of hematopoietic stem cell self-renewal and proliferation. We used murine long-term marrow cultures and a defective recombinant retrovirus vector containing the simian virus 40 large T antigen to immortalize marrow stromal cells which can support hematopoiesis in vitro for up to 5 weeks. Such cloned cell lines differentially supported stem cells which, when transplanted, allowed survival of lethally irradiated mice, formed hematopoietic spleen colonies in vivo, and stimulated lymphocyte proliferation in vitro. Molecular and functional analyses of these cell lines did not demonstrate the production of any growth factors known to support the proliferation of primitive hematopoietic stem cells. All cell lines examined produced macrophage colony-stimulating factor. The use of immortalizing retrovirus vectors may allow determination of unique cellular proteins important in hematopoietic stem cell proliferation by the systematic comparison of stromal cells derived from a variety of murine tissues.

Animals↗

PubMed1985

Deletion analysis identifies a region, upstream of the ADH2 gene of Saccharomyces cerevisiae, which is required for ADR1-mediated derepression.

Deletion analysis was used to identify sequences upstream of the ADH2 gene of Saccharomyces cerevisiae that are required for its regulation. 5' and 3' internal deletions of the ADH2 control region were created in vitro, and the fragments were ligated adjacent to the ADH1 promoter and structural gene. Hybrid genes with 3' deletions extending from -119 to -216 (the start site of ADH2 transcription is designated +1) were fully repressed and derepressed to high levels. Hybrid genes with 3' deletions extending from -119 to -257 were repressed but failed to significantly derepress. Hybrid genes lacking the -216 to -257 region also failed to respond to ADR1-5c, a mutant allele of the unlinked regulatory gene ADR1, which confers constitutive expression on ADH2. This implies that the region between these deletion endpoints, which includes a 22-base-pair sequence of dyad symmetry, is required for efficient derepression of an adjacent promoter. Internal deletions extending in the 3' direction from position -1141 confirmed these results. Deletion mutants lacking the region -1141 to -259 were normally regulated, whereas deletions extending from -1141 to -115 were not derepressible. These results support the hypotheses that the ADH2 promoter may normally be in an inactive conformation in the yeast chromosome and that derepression of ADH2 requires positive activation mediated through an upstream activation sequence located between 216 and 257 base pairs 5' to the start site of ADH2 transcription. No evidence for a DNA sequence mediating repression was obtained.

Alcohol Dehydrogenase↗

PubMed1982

Characterization of a regulatory region upstream of the ADR2 locus of S. cerevisiae.

We have used in vitro mutagenesis to identify a DNA sequence that is required for glucose regulation of the ADR2 locus of Saccharomyces cerevisiae. This region, located between 200 and 1,000 base pairs upstream of the structural gene for ADH II, has been identified by genetic and biochemical analysis as the site of ADR3, a cis-acting regulatory locus. If this region is deleted, ADR2 is no longer repressed by glucose. Moreover, if the sequence is excised and ligated in front of the ADC1 gene, it puts that gene under glucose control.

Alcohol Oxidoreductases↗

PubMedDate not supplied

The mouse Cd83 gene: structure, domain organization, and chromosome localization.

Human CD83 (hCD83) is a 45 000 Mr cell-surface protein expressed predominantly by dendritic lineage cells. In this report, the genomic locus encoding mouse CD83 (Cd83) was isolated and the gene structure determined. The Cd83 gene spans approximately 19 kilobases (kb) and is composed of five exons, with two exons encoding a single extracellular immunoglobulin (Ig)-like domain. Mouse CD83 (mCD83) cDNAs were isolated by reverse transcriptase polymerase chain reaction of mouse RNA. Sequence determination revealed substantial conservation, with mCD83 and hCD83 sharing 63% amino acid identity. The transmembrane and cytoplasmic regions of CD83 were most highly conserved. Mouse CD83 mRNA of 2.4 kb was abundantly expressed in spleen and brain, but could also be detected in most tissues analyzed. These results suggest that in the mouse, as in humans, widely distributed dendritic cells may express mCD83. Chromosome localization revealed that the Cd83 gene is present on mouse chromosome 13 band A5, while the locus for the human gene (CD83) is located within a homologous region of human chromosome 6p23. Thus, the CD83 protein and gene appear to be well conserved during recent mammalian evolution. The isolation and characterization of the mCD83 cDNA and gene provides important information and tools that will facilitate the study of CD83 and dendritic cell function in a mouse model system.

Amino Acid Sequence↗