Analysis of mammalian gene function through broad-based phenotypic screens across a consortium of mouse clinics.

The function of the majority of genes in the mouse and human genomes remains unknown. The mouse embryonic stem cell knockout resource provides a basis for the characterization of relationships between genes and phenotypes. The EUMODIC consortium developed and validated robust methodologies for the broad-based phenotyping of knockouts through a pipeline comprising 20 disease-oriented platforms.

Principles and application of LIMS in mouse clinics.

Large-scale systemic mouse phenotyping, as performed by mouse clinics for more than a decade, requires thousands of mice from a multitude of different mutant lines to be bred, individually tracked and subjected to phenotyping procedures according to a standardised schedule. All these efforts are typically organised in overlapping projects, running in parallel. In terms of logistics, data capture, data analysis, result visualisation and reporting, new challenges have emerged from such projects.

A mu-delta opioid receptor brain atlas reveals neuronal co-occurrence in subcortical networks.

Opioid receptors are G protein-coupled receptors (GPCRs) that modulate brain function at all levels of neural integration, including autonomic, sensory, emotional and cognitive processing. Mu (MOR) and delta (DOR) opioid receptors functionally interact in vivo, but whether interactions occur at circuitry, cellular or molecular levels remains unsolved. To challenge the hypothesis of MOR/DOR heteromerization in the brain, we generated redMOR/greenDOR double knock-in mice and report dual receptor mapping throughout the nervous system.

Correlation between groin pain and cup design of hip-resurfacing implants: a prospective study.

Purpose: Cup design has been incriminated as the source of groin pain after hip resurfacing but has not been well described; thus, it was assessed in a prospective study looking at three implant types.

Methods: A group-match was done between three groups of hip resurfacing devices according to age, sex, body mass index, activity level, osteoarthritis aetiology and pre-operative scores.

Results: The global groin pain rate was 5.

Metal-on-Metal Bearing: Is This the End of the Line? We Do Not Think So.

Background: Recent studies have recommended the discontinuation of metal-on-metal (MoM) components in total hip arthroplasty (THA) because of adverse effects reported with large-diameter MoM THA. This is despite favorable long-term results observed with 28 and 32 mm MoM bearings.

Questions/purposes: The aim of this study was to assess the value of calls for an end to MoM bearings as THA components.

Mouse large-scale phenotyping initiatives: overview of the European Mouse Disease Clinic (EUMODIC) and of the Wellcome Trust Sanger Institute Mouse Genetics Project.

Two large-scale phenotyping efforts, the European Mouse Disease Clinic (EUMODIC) and the Wellcome Trust Sanger Institute Mouse Genetics Project (SANGER-MGP), started during the late 2000s with the aim to deliver a comprehensive assessment of phenotypes or to screen for robust indicators of diseases in mouse mutants. They both took advantage of available mouse mutant lines but predominantly of the embryonic stem (ES) cells resources derived from the European Conditional Mouse Mutagenesis programme (EUCOMM) and the Knockout Mouse Project (KOMP) to produce and study 799 mouse models that were systematically analysed with a comprehensive set of physiological and behavioural paradigms. They captured more than 400 variables and an additional panel of metadata describing the conditions of the tests.

Cementless metal-on-metal versus ceramic-on-polyethylene hip arthroplasty in patients less than fifty years of age: a comparative study with twelve to fourteen-year follow-up.

Background: We previously reported the outcomes of a case-control study, at a minimum of five years of follow-up, comparing metal-on-metal and ceramic-on-polyethylene bearings for cementless primary hip arthroplasty in active patients below the age of fifty years. This report is an update on these groups after a minimum duration of follow-up of twelve years.

Methods: Thirty-nine metal-on-metal cementless hip replacements with a 28-mm-diameter Metasul articulation were compared with a control group that included thirty-nine cementless ceramic-on-polyethylene hip replacements performed with a 28-mm-diameter head.

Systematic gene expression mapping clusters nuclear receptors according to their function in the brain.

Nuclear receptors (NRs) compose a large family of transcription factors that operate at the interface between genes and environment, acting as sensors and effectors that translate endocrine and metabolic cues into well-defined gene expression programs. We report here on a systematic quantitative and anatomical expression atlas of the 49 NR genes in 104 regions of the adult mouse brain, organized in the interactive MousePat database. MousePat defines NR expression patterns to cellular resolution, a requirement for functional genomic strategies to understand the function of a highly heterogeneous and complex organ such as the brain.

Mouse Phenotype Database Integration Consortium: integration [corrected] of mouse phenome data resources.

Understanding the functions encoded in the mouse genome will be central to an understanding of the genetic basis of human disease. To achieve this it will be essential to be able to characterize the phenotypic consequences of variation and alterations in individual genes. Data on the phenotypes of mouse strains are currently held in a number of different forms (detailed descriptions of mouse lines, first-line phenotyping data on novel mutations, data on the normal features of inbred lines) at many sites worldwide.