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C Bieberich

Publications and source records attributed to C Bieberich.

13 recordsLinked to original sources
PubMed2001

Influence of neonatal estrogens on rat prostate development.

Brief exposure of rodents to estrogens during early development alters prostate branching morphogenesis and cellular differentiation in a dose-dependant manner. If estrogenic exposures are high, these disturbances lead to permanent imprints of the prostate, which include reduced growth, differentiation defects of the epithelial cells, altered secretory function and reduced responsiveness to androgens in adulthood. This process, referred to as neonatal imprinting or developmental estrogenization, is associated with an increased incidence of prostatic lesions with aging, which include hyperplasia, inflammation and dysplasia. To better understand how early estrogenic exposures can permanently alter prostate growth and function and predispose the gland to neoplasia, the effects of estrogens on prostatic steroid receptors, cell-cell communication molecules and key developmental genes were examined. Transient and permanent alterations in the expression of prostatic androgen receptors, estrogen receptors alpha (ERalpha) and beta, and retinoic acid receptors are observed. It is proposed that the estrogen-induced alterations in these critical transcription factors play a fundamental role in initiating prostatic growth and differentiation defects. Down-stream effects of the altered steroid receptor expression include disruption of TGFbeta paracrine communication, altered expression of gap junction connexin molecules and loss of epithelial cadherin on epithelial cells. Additionally, specific disruptions in the expression of prostatic developmental genes are observed in response to neonatal estrogen. An extended developmental period of hoxa-13 expression, a lack of hoxd-13 increase with maturation, and an immediate and sustained suppression of hoxb-13 was noted within prostatic tissue. A transient decrease in Nkx3.1 expression in the developing prostate was also observed. Thus subtle and overt alterations in Hox-13 and Nkx3.1 genes may be involved in the altered prostate phenotype in response to neonatal estrogen exposure. In summary, estrogen imprinting of the prostate gland is mediated through up-regulated levels of stromal ERalpha, which initiates alterations in steroid receptor expression within the developing gland. Rather than being an androgen-dominated process, as occurs normally, prostatic development is regulated by alternate steroids, including estrogens and retinoids, in the estrogenized animal. This, in turn, leads to disruptions in the coordinated expression of critical developmental genes including TGFbeta, Hox-13 genes and Nkx3.1. Since a precise temporal expression pattern of these and other molecules is normally required for appropriate differentiation of the prostatic epithelium and stroma, the estrogen-initiated disruption in this pattern would lead to permanent differentiation defects of the prostate gland. It is hypothesized that these molecular and cellular changes initiated early in life predispose the prostate to the neoplastic state upon aging.

Animals↗
PubMed2000

Differential effects on T cell and NK cell development by tissue-specific expression of H-2D(d) transgene.

The effect of tissue-specific expression of the MHC class I molecule H-2D(d) on T cell and NK cell specificity was studied in transgenic mice expressing the H-2D(d) gene under the control of the mouse metallothionein-I promoter. MTD mice expressed high amounts of H-2D(d) in the liver, intestine and testis, but only minute amounts in the thymus, spleen and kidney. Zinc administration resulted in a 1.5- and 8.5-fold increase in H-2D(d) expression in the liver and the intestine, respectively, but did not affect expression in the other organs tested. T cell tolerance developed towards H-2D(d) in MTD mice, even in the absence of zinc. In contrast, NK cell-mediated natural resistance against lymphoma grafts was not seen in MTD mice, despite zinc administration. NK cells in MTD mice also failed to develop self tolerance to H-2D(d). The lack of functional effects did not result from inability of NK cells in MTD mice to interact with H-2D(d), as down-regulation of Ly49A receptor expression was observed on liver NK cells in MTD mice. Our data reveal a difference between T cells and NK cells in their requirements for MHC class I molecules in specificity development.

Animals↗
PubMed1997

Natural killer cell tolerance in mice with mosaic expression of major histocompatibility complex class I transgene.

We have studied natural killer (NK) cell tolerance in a major histocompatibility complex (MHC) class I transgenic line, DL6, in which the transgene product was expressed on only a fraction of blood cells. In contrast with transgenic mice expressing the same transgene in all cells, NK cells from mosaic mice failed to reject transgene-negative bone marrow or lymphoma grafts. However, they retained the capability to reject cells with a total missing-self phenotype, i.e., cells lacking also wild-type MHC class I molecules. Tolerance against transgene-negative cells was demonstrated also in vitro, and could be broken if transgene-positive spleen cells of mosaic mice were separated from negative cells before, or after 4 d of culture in interleukin-2. The results provide support for selective NK cell tolerance to one particular missing-self phenotype but not to another. We suggest that this tolerance is determined by NK cell interactions with multiple cells in the environment, and that it is dominantly controlled by the presence of cells lacking a specific MHC class I ligand. Furthermore, the tolerant NK cells could be reactivated in vitro, which suggests that the tolerance occurs without deletion of the potentially autoreactive NK cell subset(s), and that it may be dependent upon the continuous presence of tolerizing cells.

Animals↗
PubMed1990

Structural analysis of the Hox-3.1 transcription unit and the Hox-3.2--Hox-3.1 intergenic region.

The mouse Hox gene family is a set of mammalian homeobox genes that may represent developmental control genes. Complete information about the primary structure of these genes is a prerequisite for a systematic analysis of the mechanisms that determine their complex tempero-spatial expression patterns. In this report we describe the complete sequence of the Hox-3.1 locus and provide evidence for several closely spaced transcriptional start sites. Sequence analysis of the 5' region of the Hox-3.1 gene extending to its nearest upstream neighbor, Hox-3.2, allowed us to identify sequences known to be capable of interactions with transcription factors. Several of these sequence motifs are similar to cis-regulatory elements found in the regulatory regions of other known developmentally regulated genes.

Amino Acid Sequence↗
PubMed1989

Prevention of allogeneic bone marrow graft rejection by H-2 transgene in donor mice.

Rejection of bone marrow grafts in irradiated mice is mediated by natural killer (NK) cells and is controlled by genes linked to the major histocompatibility complex (MHC). It has, however, not been possible to identify the genes or their products. An MHC class I (Dd) transgene introduced in C57BL donors prevented the rejection of their bone marrow by NK cells in irradiated allogeneic and F1 hybrid mice expressing the Dd gene. Conversely, H-2Dd transgenic C57BL recipients acquired the ability to reject bone marrow from C57BL donors but not from H-2Dd transgenic C57BL donors. These results provide formal evidence that NK cells are part of a system capable of rejecting cells because they lack normal genes of the host type, in contrast to T cells, which recognize cells that contain abnormal or novel sequences of non-host type.

Animals↗
PubMed1989

The visna virus long terminal repeat directs expression of a reporter gene in activated macrophages, lymphocytes, and the central nervous systems of transgenic mice.

Visna virus is a lentivirus which causes a slow progressive disease involving the immune system and the central nervous system. To determine the role of the viral long terminal repeat (LTR) in targeting the virus to specific host cells and tissues, transgenic mice were constructed which contained the visna virus LTR directing expression of the bacterial gene encoding chloramphenicol acetyltransferase (CAT). Analysis of the transgenic mouse tissues for CAT activity revealed that the viral LTR was responsible, in part, for the tropism of visna virus for macrophages and the central nervous system. Expression of the LTR required the macrophage to be in an activated state both in vivo and in vitro. Thioglycolate activation of peritoneal macrophages in vivo and 12-O-tetradecanoylphorbol 13-acetate treatment in vitro induced expression of the visna virus LTR. Lymphocytes from the spleens of the transgenic mice expressed CAT activity, suggesting that visna virus was able to replicate in lymphocytes, as did human immunodeficiency virus and simian immunodeficiency virus. These studies demonstrated that the lentivirus LTR was responsible, in part, for cell and tissue tropism in vivo.

Animals↗
PubMed1988

Natural resistance against lymphoma grafts conveyed by H-2Dd transgene to C57BL mice.

The H-2Dd transgenic strain D8 on C57BL background was more resistant to subcutaneous challenge of RBL-5 lymphoma cells than B6 controls. The direct role of the H-2Dd antigen was investigated by the use of (D8 x B6)F1 crosses and (D8 B6) x B6 backcrosses. The latter showed cosegregation with regard to Dd antigen expression and lymphoma resistance, both of which were inherited in a pattern consistent with control by a single dominant gene. The rejection potential in (D8 x B6)F1 mice appeared as strong as that seen in crosses between B6 and MHC congenic mice (on B10 background) carrying H-2Dd. The lymphoma resistance could be abrogated by treatment with anti-asialo GM1 antiserum or anti-NK 1.1 mAb, indicating a role for NK cells.

Animals↗
PubMed1987

A transgenic class I antigen is recognized as self and functions as a restriction element.

The function of a transgenic Dd class I molecule in the induction of immunologic tolerance to major histocompatibility complex antigens and in directing major histocompatibility complex restriction in C57BL/6 mice were investigated. All of the transgenic Dd mouse strains were found to be tolerant for the Dd antigen. Spleen cells from transgenic mice were immunocompetent but consistently failed to generate an anti-Dd cytotoxic T lymphocyte response in vitro, and skin grafts between transgenic Dd mice were not rejected. These data suggests that the Dd antigen was recognized as a self molecule. In addition, the transgenic Dd mice generated antigen-specific Dd-restricted cytotoxic T lymphocyte, indicating that the Dd antigen also functioned as a restriction element for antigen recognition. These observations demonstrate the usefulness of the transgenic mouse system for studying class I antigen expression and function.

Animals↗
PubMed1987

Functional expression of a heterologous major histocompatibility complex class I gene in transgenic mice.

The regulated expression of major histocompatibility complex class I antigens is essential for assuring proper cellular immune responses. To study H-2 class I gene regulation, we have transferred a foreign class I gene to inbred mice and have previously shown that the heterologous class I gene was expressed in a tissue-dependent manner. In this report, we demonstrate that these mice expressed the transgenic class I molecule on the cell surface without any alteration in the level of endogenous H-2 class I antigens. Skin grafts from transgenic mice were rapidly rejected by mice of the background strain, indicating that the transgenic antigen was expressed in an immunologically functional form. As with endogenous H-2 class I genes, the class I transgene was inducible by interferon treatment and suppressible by human adenovirus 12 transformation. Linkage analysis indicated that the transgene was not closely linked to endogenous class I loci, suggesting that trans-regulation of class I genes can occur for class I genes located outside the major histocompatibility complex.

Animals↗
PubMed1986

Regulated expression of a murine class I gene in transgenic mice.

The major histocompatibility complex class I genes play an essential role in the immune presentation of aberrant cells. To gain further insight into the regulation of the expression of these class I genes and to better define the functions of their protein products, we made use of the technique of gene transfer into the germ line of inbred mice. With the use of locus-specific DNA probes, we observed that a transgenic class I gene was expressed in a tissue-dependent fashion analogous to that of an endogenous class I gene. In addition, the level of expression of the transgenic gene was substantially higher that that of the endogenous gene. The availability of transgenic mice properly expressing a foreign murine class I gene provides a unique system to further define the role of the class I antigens in the maturation of the immune response and in determining the malignant and metastatic phenotypes of tumor cells.

Animals↗