Biomedical subjects

I Renner-Müller

Publications and source records attributed to I Renner-Müller.

8 recordsLinked to original sources

PubMed2004

Peri/nuclear localization of intact insulin-like growth factor binding protein-2 and a distinct carboxyl-terminal IGFBP-2 fragment in vivo.

Insulin-like growth factor binding protein-2 (IGFBP-2) as one of the most important IGFBPs has never been assessed in the intracellular compartment in vivo. Since there is evidence for novel intracellular functions of distinct IGFBPs, we investigated the presence of IGFBP-2 inside the cell. In peri/nuclear fractions of various tissues isolated from IGFBP-2 transgenic and non-transgenic mice we were able to show the presence of intact IGFBP-2. In addition, we demonstrate the presence of a highly conserved carboxyl-terminal IGFBP-2 fragment in the peri/nuclear fraction by using different peptide-induced antibodies. In pancreatic sections, confocal microscopy revealed the presence of IGFBP-2 on the nuclear surface but not within the nucleus. Our findings suggest novel functions of intact IGFBP-2 and IGFBP-2 fragments within the cell.

Amino Acid Sequence↗

PubMed2002

Mutation of the RGD sequence does not affect plasma membrane association and growth inhibitory effects of elevated IGFBP-2 in vivo.

Using insulin-like growth factor-binding protein-2 (IGFBP-2) transgenic mice (D mice) as a model of elevated IGFBP-2 expression, which is often found in unphysiological conditions, we found association of IGFBP-2 to purified plasma membranes of many organs. To determine whether the RGD (Arg-Gly-Asp) motif of IGFBP-2 mediates cell surface binding in vivo, we mutated the RGD motif of IGFBP-2 into an RGE (Arg-Gly-Glu) sequence and produced transgenic mice (E mice) which express elevated amounts of mutated IGFBP-2. Our data demonstrate that in vivo IGFBP-2 cell surface association is not dependent on the RGD motif and that mutation of this sequence does not alter growth inhibitory effects of IGFBP-2.

Amino Acid Motifs↗

PubMed2000

Contrasting obesity phenotypes uncovered by partial leptin receptor gene deletion in transgenic mice.

Non-insulin-dependent diabetes mellitus (type 2 diabetes) is known to be a polygenic and polyfactorial disorder. Here we describe the long-term examination of a transgenic mouse line showing the disruption of the leptin receptor (Lepr, Ob-R) gene caused by transgene insertion. The absence of the expression of the long isoform Ob-Rb uncovered a strong variation of the obesity and diabetes phenotype in the homozygous mutant mice of the outbred strain used. One part of the homozygous mice developed severe persistent early-onset obesity, whereas the other part developed cachexia after having shown initial obesity in the examination period up to 26 weeks p.p. The leptin-receptor-defective mice of this line might serve as a model for the investigation of genes modulating the development and mode of expression of diabetes.

Animals↗

PubMed2000

Large-scale N-ethyl-N-nitrosourea mutagenesis of mice--from phenotypes to genes.

The most important tool for obtaining insight into the function of genes is the use of mutant model organisms. Homologous recombination in embryonic stem cells allows the systematic production of mouse mutants for any gene that has been cloned. Gene trap strategies have been designed to interrupt even unknown genes which are tagged by the inserted vector and can be characterised structurally and functionally. Complementary to such 'gene-driven' approaches, 'phenotype-driven' approaches are necessary to identify new genes or gene products through a search for mutants with specific defects, uncovering the function of genetic pathways in physiological and pathological processes. Mutagenesis using the alkylating agent N-ethyl-N-nitrosourea (ENU) is a powerful approach for the production of such mouse mutants. Since ENU induces mainly point mutations in premeiotic spermatogonia, this strategy allows the production of multiple alleles of a particular gene, which is pivotal for a fine tuned analysis of its function.

Alkylating Agents↗

PubMed1999

CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs.

The proper function of immune surveillance requires well-coordinated mechanisms in order to guide the patrolling immune cells through peripheral tissues and into secondary lymphoid organs. Analyzing gene-targeted mice, we identified the chemokine receptor CCR7 as an important organizer of the primary immune response. CCR7-deficient mice show severely delayed kinetics regarding the antibody response and lack contact sensitivity and delayed type hypersensitivity reactions. Due to the impaired migration of lymphocytes, these animals reveal profound morphological alterations in all secondary lymphoid organs. Upon activation, mature skin dendritic cells fail to migrate into the draining lymph nodes. Thus, in order to bring together lymphocytes and dendritic cells to form the characteristic microarchitecture of secondary lymphoid organs, CCR7 is required to rapidly initiate an adoptive immune response.

Animals↗

PubMed1999

A non-destructive technique for 3-D microstructural phenotypic characterisation of bones in genetically altered mice: preliminary data in growth hormone transgenic animals and normal controls.

A non-destructive, three-dimensional technique for microstructural phenotypic characterisation of skeletal elements in genetically altered mice is presented. Preliminary data in bovine growth-hormone transgenic animals and control littermates are shown. The technique is based on microcomputed tomography (microCT) and digital postprocessing and allows for a differential quantitative analysis of the cortical and trabecular bone compartments in the axial and peripheral skeleton. The distal femora and the first lumbar vertebral bodies of six animals were CT scanned in the axial plane with an isotropic resolution of 20 microm. The periostal surface and the marrow spaces were segmented fully automatically, and the trabecular and cortical compartments were separated interactively. After 3-D reconstruction, various regions of interest (diaphyseal, metaphyseal and epiphyseal) were selected for the analysis. The femora and vertebrae of the transgenic animals showed obvious differences in size, shape, and trabecular arrangement compared with the control animals. The total bone mass was increased by a factor of two to three, but the trabecular bone was increased much more (up to 12 times) than the cortical bone. The transgenic animals showed an increased ratio of trabecular vs cortical bone (0.90 to 1.27 vs 0.14 to 0.36 in the femoral diaphysis) and an elevated trabecular bone volume fraction (49% to 73% vs 18% to 43% in the femoral metaphysis). The mean 3-D cortical thickness was similar in the normal and transgenic animals (values between 93 microm and 232 microm in the dia- and metaphyses), but the minimal cortical thickness was lower in the transgenic animals (22 to 31 microm vs 54 microm to 110 microm in the diaphysis). The technique presented is suitable for phenotypic characterisation of bone structure in genetically altered mice.

Animals↗

PubMed1999

[Sex-specific analysis of bone mass in normal and growth hormone transgenic mice using dual energy x-ray absorptiometry (DXA)].

The aim of the present study was the non-invasive, sex-specific measurement of bone mass in bovine growth hormone (bGH) transgenic mice and normal controls with dual energy X-ray absorptiometry (DXA). The transgenic mouse constitutes a suitable animal model to study the influence of growth hormone on the skeletal system. We analysed 28 animals, aged 12 weeks (14 transgenic, 14 controls, 7 male and 7 female, respectively), using a peripheral DXA scanner that had been adapted to the measurement of small animals. At a measurement time of 20 min, the precision (RMS average CV%) was 4.4% for bone mass (BMC), 2.5% for areal bone density (BMD), 0.86% for total body weight and 4.5% for the percentage BMC (relative to body weight). While the absolute bone mass was not significantly different between male and female animals, we found a higher percentage of the BMC relative to the total bone mass in females (+21% in controls, +31% in transgenics; p < 0.01). The absolute bone mass was higher in the transgenic animals (+71% in females and +62% in males; p < 0.01), but relative to the body weight the transgenic females yielded similar and the transgenic males lower values (-7.2%; p < 0.05). Using DXA it is possible to non-invasively determine the mass of mineralised tissue in the mouse with relatively high precision and to effectively discriminate between different groups. Although a strong influence of growth hormone on the absolute bone mass is observed, the results show that this increase is not higher than that of the total body mass.

Absorptiometry, Photon↗

PubMed1999

Overgrowth of skin in growth hormone transgenic mice depends on the presence of male gonads.

Growth hormone has been shown to possess stimulatory effects on various connective tissues. We observed that skin growth in male rat phosphoenolpyruvate carboxykinase-bovine growth hormone transgenic mice (serum growth hormone levels: 740-1940 ng per ml) is progressive with age, resulting in an "oversized coat" phenotype with a marked increase in absolute and relative skin weight and surface area, and in thickness of the dermis. Histologic changes include severe dermal fibrosis and replacement of subdermal adipose tissue by fibrous tissue. Apart from an increase in skin surface area, these changes were not noted in female transgenic mice, arguing for a specific interaction of growth hormone with male sex hormones. To clarify this point, 6 wk old male transgenic mice and control mice were castrated and compared with their noncastrated counterparts in parameters of skin growth at an age of 8 mo. The skin weight of castrated transgenic mice was smaller (p < 0.01) than that of intact transgenic mice both absolutely and relative to body weight. The relative skin weight of castrated transgenic mice was in the same range as in intact and castrated control mice. Absolute and relative skin area of castrated transgenic mice was greater (p < 0. 001 and p < 0.05) than in controls but lower than in intact transgenic mice (p < 0.001 and p < 0.05). When compared with control mice, intact transgenic mice displayed an increase (p < 0.01) in the thickness of dermis. In castrated transgenic mice the thickness of the dermis was in the same range as in control mice. Our findings demonstrate a specific interaction of growth hormone with male sex hormones resulting in a marked stimulation of skin growth.

Androgens↗