Sex- and age-dependent effects of Gpr30 genetic deletion on the metabolic and cardiovascular profiles of diet-induced obese mice.

The G protein-coupled receptor 30 (GPR30) has been claimed as an estrogen receptor. However, the literature reports controversial findings and the physiological function of GPR30 is not fully understood yet. Consistent with studies assigning a role of GPR30 in the cardiovascular and metabolic systems, GPR30 expression has been reported in small arterial vessels, pancreas and chief gastric cells of the stomach.

A novel N-ethyl-N-nitrosourea-induced mutation in phospholipase Cγ2 causes inflammatory arthritis, metabolic defects, and male infertility in vitro in a murine model.

Objective: It is difficult to identify a single causative factor for inflammatory arthritis because of the multifactorial nature of the disease. This study was undertaken to dissect the molecular complexity of systemic inflammatory disease, utilizing a combined approach of mutagenesis and systematic phenotype screening in a murine model.

Methods: In a large-scale N-ethyl-N-nitrosourea mutagenesis project, the Ali14 mutant mouse strain was established because of dominant inheritance of spontaneous swelling and inflammation of the hind paws.

Features and strategies of ENU mouse mutagenesis.

Aim of this review is to demonstrate the relevance of animal models created by ENU mutagenesis for the pharmaceutical community to understand diseases and the modulation of disease status by pharmaceutical compounds. We give an overview of what ENU mutagenesis in mice implies and introduce the main research centers running ENU mutagenesis projects. The different strategies of ENU mutagenesis screens are explained as well as the latest advances in mapping and mutation detection strategies, which until recently have been the main limiting step in forward genetics/phenotype-driven approaches.

Expression pattern of G protein-coupled receptor 30 in LacZ reporter mice.

Multiple reports implicated the function of G protein-coupled receptor (GPR)-30 with nongenomic effects of estrogen, suggesting that GPR30 might be a G-protein coupled estrogen receptor. However, the findings are controversial and the expression pattern of GPR30 on a cell type level as well as its function in vivo remains unclear. Therefore, the objective of this study was to identify cell types that express Gpr30 in vivo by analyzing a mutant mouse model that harbors a lacZ reporter (Gpr30-lacZ) in the Gpr30 locus leading to a partial deletion of the Gpr30 coding sequence.

Mutation in a novel connexin-like gene (Gjf1) in the mouse affects early lens development and causes a variable small-eye phenotype.

Purpose: The purpose of the study was the characterization of the novel small-eye mutant Aey12 in the mouse.

Methods: The eyes of the mutants were described morphologically and histologically and by in situ hybridization.

Results: The homozygotes were viable and fully fertile, which identifies Aey12 as a new microphthalmia phenotype in the mouse, different from Maf or Pax6 mutants.

A phenotype-driven ENU mutagenesis screen for the identification of dominant mutations involved in alcohol consumption.

The aim of this study was the application of a phenotype-driven N-ethyl-N-nitrosourea (ENU) mutagenesis screen in mice for the identification of dominant mutations involved in the regulation and modulation of alcohol-drinking behavior. The chemical mutagen ENU was utilized in the generation of 131 male ENU-mutant C57BL/6J mice (G0). These ENU-treated mice were paired with wild-type C57BL/6J mice to generate G1 and subsequent generations.

Novel mouse mutants with primary cellular immunodeficiencies generated by genome-wide mutagenesis.

Background: Primary cellular immunodeficiencies are a group of genetic disorders in which 1 or more components of the cellular immune system are lacking or dysfunctional.

Objective: We sought to identify novel mouse mutants that display primary cellular immunodeficiencies.

Methods: Genome-wide N-ethyl-N-nitrosourea mutagenesis was performed in mice, followed by a phenotype screen of immunologic blood parameters.

A genetic screen for modifiers of the delta1-dependent notch signaling function in the mouse.

The Notch signaling pathway is an evolutionarily conserved transduction pathway involved in embryonic patterning and regulation of cell fates during development. Recent studies have demonstrated that this pathway is integral to a complex system of interactions, which are also involved in distinct human diseases. Delta1 is one of the known ligands of the Notch receptors.

Three novel Pax6 alleles in the mouse leading to the same small-eye phenotype caused by different consequences at target promoters.

Purpose: To characterize three new mouse small-eye mutants detected during ethylnitrosourea mutagenesis programs.

Methods: Three new mouse small-eye mutants were morphologically characterized, particularly by in situ hybridization. The mutations were mapped, and the candidate gene was sequenced.

Electroretinography as a screening method for mutations causing retinal dysfunction in mice.

Purpose: To detect mice with hereditary retinal impairment, a high-throughput electroretinography (ERG) screening system was established.

Method: Mice from eight different strains without known retinal disorders (102, 129/SvJ, AKR, C57BL/6J, C57BL/6JIco, CBA/CaJ, and DBA/2NCrlBR) and one control strain with retinal degeneration (C3HeB/FeJ) were fixed on a specially constructed sled, ERG electrodes were placed on the cornea, and mice were moved into a Ganzfeld stimulator. From a luminance range of 0.

V76D mutation in a conserved gD-crystallin region leads to dominant cataracts in mice.

During a large-scale ENU mutagenesis screen, a mouse mutant with a dominant cataract was detected and referred to as Aey4. Aim of this study was the morphological description of the mutant, the mapping of the mutation, and the characterization of the underlying molecular lesion. The slit-lamp examination revealed a strong nuclear cataract surrounded by a homogeneous milky opacity in the inner cortex.