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Progress in a replicated selection for elevated blood ethanol concentrations in HDID mice.

ABSTRACT: Drinking in the dark (DID) is a limited access ethanol-drinking phenotype in mice. High Drinking in the Dark (HDID-1) mice have been bred for 27 selected generations (S27) for elevated blood ethanol concentrations (BECs) after a 4-h period of access to 20% ethanol. A second replicate line (HDID-2) was started later from the same founder population and is currently in S20. An initial report of response to selection in HDID-1 was published after S11. This article reports genetic and behavioral characteristics of both lines in comparison with the HS controls. Heritability is low in both replicates (h(2) ?=?0.09) but the lines have shown 4-5 fold increases in BEC since S0; 80% of HDID-1 and 60% of HDID-2 mice reach BECs greater than 1.0?mg/ml. Several hours after a DID test, HDID mice show mild signs of withdrawal. Although not considered during selection, intake of ethanol (g/kg) during the DID test increased by approximately 80% in HDID-1 and 60% in HDID-2. Common genetic influences were more important than environmental influences in determining the similarity between BEC and intake for HDID mice. Analysis of the partitioning of intake showed that 60% of intake is concentrated in the last 2?h of the 4?h session. However, this has not changed during selection. Hourly BECs during the DID test reach peak levels after 3 or 4?h of drinking. HDID mice do not differ from HS mice in their rate of elimination of an acute dose of alcohol.

SUBMITTER: Crabbe JC

PROVIDER: S-EPMC3923418 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Progress in a replicated selection for elevated blood ethanol concentrations in HDID mice.

Crabbe J C JC Metten P P Belknap J K JK Spence S E SE Cameron A J AJ Schlumbohm J P JP Huang L C LC Barkley-Levenson A M AM Ford M M MM Phillips T J TJ

Genes, brain, and behavior 20131206 2

Drinking in the dark (DID) is a limited access ethanol-drinking phenotype in mice. High Drinking in the Dark (HDID-1) mice have been bred for 27 selected generations (S27) for elevated blood ethanol concentrations (BECs) after a 4-h period of access to 20% ethanol. A second replicate line (HDID-2) was started later from the same founder population and is currently in S20. An initial report of response to selection in HDID-1 was published after S11. This article reports genetic and behavioral cha ...[more]

PMID: 24219304

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Project description:To determine whether elevated blood cobalt (Co) concentrations are associated with early failure of metal-on-metal (MoM) hip resurfacings secondary to adverse reaction to metal debris (ARMD).Cohort study.Single centre orthopaedic unit.Following the identification of complications potentially related to metal wear debris, a blood metal ion screening programme was instigated at our unit in 2007 for all patients with Articular Surface Replacement (ASR) and Birmingham MoM hip resurfacings. Patients were followed annually unless symptoms presented earlier. Symptomatic patients were investigated with ultrasound scan and joint aspiration. The clinical course of all 278 patients with 'no pain' or 'slight/occasional' pain and a Harris Hip Score greater than or equal to 95 at the time of venesection were documented. A retrospective analysis was subsequently conducted using mixed effect modelling to investigate the temporal pattern of blood Co levels in the patients and survival analysis to investigate the potential role of case demographics and blood Co levels as risk factors for subsequent failure secondary to ARMD.Blood Co concentration was a positive and significant risk factor (z=8.44, p=2×10(-16)) for joint failure, as was the device, where the Birmingham Hip Resurfacing posed a significantly reduced risk for revision by 89% (z=-3.445, p=0.00005 (95% CI on risk 62 to 97)). Analysis using Cox-proportional hazards models indicated that men had a 66% lower risk of joint failure than women (z=-2.29419, p=0.0218, (95% CI on risk reduction 23 to 89)).The results suggest that elevated blood metal ion concentrations are associated with early failure of MoM devices secondary to adverse reactions to metal debris. Co concentrations greater than 20 µg/l are frequently associated with metal staining of tissues and the development of osteolysis. Development of soft tissue damage appears to be more complex with females and patients with ASR devices seemingly more at risk when exposed to equivalent doses of metal debris.

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Progress in a replicated selection for elevated blood ethanol concentrations in HDID mice.

Publications

Progress in a replicated selection for elevated blood ethanol concentrations in HDID mice.

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