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R Behringer

Publications and source records attributed to R Behringer.

16 recordsLinked to original sources
PubMed2001

Differences in tissue-specific and embryonic expression of mouse Ceacam1 and Ceacam2 genes.

The intercellular adhesion molecule CEACAM1, also known as C-CAM1 (where CAM is cell-adhesion molecule), can function as a tumour suppressor in several carcinomas, including those of the prostate, breast, bladder and colon. This suggests that CEACAM1 may play an important role in the regulation of normal cell growth and differentiation. However, there is no direct evidence to support this putative function of CEACAM1. To elucidate its physiological function by targeted gene deletion, we isolated the Ceacam genes from a mouse 129 Sv/Ev library. Although there is only one Ceacam1 gene in humans and one in rats, two homologous genes (Ceacam1 and Ceacam2) have been identified in the mouse. Our sequence analysis revealed that the genes encoded nine exons and spanned approx. 16-17 kb (Ceacam1) and 25 kb (Ceacam2). The genes were highly similar (79.6%). The major differences in the protein-coding regions were located in exons 2, 5 and 6 (76.9%, 87.0% and 78.5% similarity respectively). In addition, introns 2, 5 and 7 were also significantly different, being 29.7%, 59.8% and 64.5% similar respectively. While most of these differences were due to nucleotide substitutions, two insertions of 418 and 5849 bp occurred in intron 2 of Ceacam2, and another two insertions of 1384 and 197 bp occurred in introns 5 and 7 respectively. To determine whether functional redundancy exists between Ceacam1 and Ceacam2, we examined their expression in 16 mouse tissues by using semi-quantitative reverse transcription-PCR. As in human and rat, in the mouse Ceacam1 mRNA was highly abundant in the liver, small intestine, prostate and spleen. In contrast, Ceacam2 mRNA was only detected in kidney, testis and, to a lesser extent, spleen. Reverse transcription-PCR using testis RNA indicated that Ceacam2 in the testis is an alternatively spliced form containing only exons 1, 2, 5, 6, 8 and 9. In the mouse embryo, Ceacam1 mRNA was detected at day 8.5, disappeared between days 9.5 and 12.5, and re-appeared at day 19. On the other hand, no Ceacam2 mRNA was detected throughout embryonic development. The different tissue expression patterns and regulation during embryonic development suggest that the CEACAM1 and CEACAM2 proteins, although highly similar, may have different functions both during mouse development and in adulthood.

Adenosine Triphosphatases↗
PubMed2001

The allocation and differentiation of mouse primordial germ cells.

Analysis of the lineage potency of epiblast cells of the early-streak stage mouse embryo reveals that the developmental fate of the cells is determined by their position in the germ layer. Epiblast cells that are fated to become neuroectoderm can give rise to primordial germ cells (PGCs) and other types of somatic cells when they were transplanted to the proximal region of the epiblast. On the contrary, proximal epiblast cells transplanted to the distal region of the embryo do not form PGCs. Therefore, the germ line in the mouse is unlikely to be derived from a predetermined progenitor population, but may be specified as a result of tissue interactions that take place in the proximal epiblast of the mouse gastrula. The initial phase of the establishment of the PGC population requires, in addition to BMP activity emanating from the extraembryonic ectoderm, normal Lim1 and Hnf3beta activity in the germ layers. The entire PGC population is derived from a finite number of progenitor cells and there is no further cellular recruitment to the germ line after gastrulation. The XX PGCs undergo X-inactivation at the onset of migration from the gut endoderm and re-activate the silenced X-chromosome when they enter the urogenital ridge. Germ cells that are localised ectopically in extragonadal sites do not re-activate the X-chromosome, even when nearly all germ cells in the fetal ovary have restored full activity of both X-chromosomes. XXSxr germ cells can re-activate the X-chromosome in the sex-reversed testis, suggesting that the regulation of X-chromosome activity is independent of ovarian morphogenesis.

Animals↗
PubMed2000

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Journal Article↗
PubMed1991

Expression of mouse IgA by transgenic mice, pigs and sheep.

The development of transgenic animal technology allows the introduction of desired traits into the germ line of mice and other animals. Since the production of antibody to various polysaccharide antigens can be protective against pathogenic bacteria, we generated transgenic mice, sheep and pigs carrying genes encoding the mouse alpha and kappa chains for antibodies against phosphorylcholine (PC) to determine whether transgene antibody might be used to influence susceptibility to disease. High serum levels of mouse IgA were detected in transgenic mice and pigs but not in transgenic sheep. It has been noted that transgene immunoglobulin expression can suppress endogenous immunoglobulin gene rearrangement and expression, and indeed, in one mouse line, expression of the transgene resulted in less than 10% of spleen B cells expressing endogenous IgM. Despite this suppression, significant levels of endogenous IgM were still secreted into the serum. Suppression of endogenous IgM expression was not seen in other mouse lines, nor was it seen in transgenic pigs. In the transgenic pigs, the mouse IgA was detected in the serum despite the absence of an intact mouse kappa transgene, so the secreted antibody presumably included pig light chains. Little if any of the mouse IgA in these sera showed binding specificity for PC. In one of the founder sheep, mouse IgA was detectable in peripheral lymphocytes but not in serum. Mouse kappa expression was not detected in the transgenic sheep harboring an intact kappa transgene. These results illustrate the potential of introducing beneficial traits such as germ-line-encoded immunity into large mammalian species.

Animals↗
PubMed1988

Progressive glomerulosclerosis develops in transgenic mice chronically expressing growth hormone and growth hormone releasing factor but not in those expressing insulinlike growth factor-1.

An increase in glomerular size occurs in normal maturation after subtotal renal ablation and disease states such as diabetes mellitus. The role that growth hormone (GH), growth hormone releasing factor (GHRF), and insulinlike growth factor-1 (IGF-1) play in these processes has been investigated using transgenic mice chronically expressing these hormones. The glomeruli were enlarged in all 3 strains of mice. Mesangial proliferation followed by progressive glomerulosclerosis was observed in the GH and GHRF animals only. In the IGF-1 mice the large glomeruli remained morphologically normal except for the enlargement. These data suggest that the glomerulosclerosis was due, in part, to disordered mesangial cell growth in response to circulating GH. The mesangial lesions in mice with chronically high plasma GH levels mimicked those in human diabetes mellitus. These models provide a means to study the hormonal regulation of glomerular growth and the role that specific hormones might play in the pathogenesis of glomerulosclerosis.

Animals↗
PubMed1983

Protease activity associated with loss of adhesiveness in mouse teratocarcinoma.

We have observed the spontaneous conversion of an embryoid body (multicellular) form of 129/J mouse ascites teratocarcinoma to a single cell form. Concomitant with the conversion, a rapid increase in growth rate and ascites fluid accumulation have been observed. This report presents data on protease activity in the ascites fluid after the conversion and evidence that the protease causes decreased tumor cell adhesiveness. Ascites protease has a pH optimum of 2.0-3.0 and is inhibited by both DAN (diazoacetyl-DL-norleucine methyl ester) and Pepstatin A. Using denatured bovine hemoglobin as a substrate, the low pH optimum and inhibition by DAN and Pepstatin A allow tentative identification of the enzyme as the carboxypeptidase Cathepsin D. Approx. 0.036 X 10(-2) micrograms of Cathepsin D per mg of protein was found in the ascites fluid of the single cell form of the mouse teratocarcinoma. We show that Pepstatin A-derivatized agarose beads bind the single ascites cells, causing them to display increased cell-cell adhesion, a phenomenon not observed with control beads. The results suggest that ascites protease may play a role in transformation of a slow growing, clustered tumor into a rapidly growing, non-adhesive, single cell form. We found that an embryoid-like tissue culture line of mouse teratocarcinoma, that we established, disaggregated into single cells, upon addition of ascites fluid from the single cell tumor, to the culture medium. Pepstatin A prevented disaggregation of the cell clusters. These results further support the contention that specific ascites protease plays a role in the transformation of a clustered tumor into a single cell form.

Animals↗