Article

Screening for ENU-induced mutations in mice that result in aberrant ethanol-related phenotypes

Department of Psychology, The University of Memphis, Memphis, Tennessee, United States
Behavioral Neuroscience (Impact Factor: 3.25). 09/2007; 121(4):665-78. DOI: 10.1037/0735-7044.121.4.665
Source: PubMed

ABSTRACT One way to investigate the genetic underpinnings of ethanol-related phenotypes is to create random mutations and screen the mutagenized mice for their behavioral phenotypes. The purposes of this article are to assess the efficacy of a novel high throughput screen to detect known strain differences and to provide evidence of the ability of this screen to detect phenodeviants, as illustrated by two new lines of mutant mice. All mice were tested for the following phenotypes after a dose of 2.25 g/kg of ethanol: ataxia, anxiolytic response, locomotor activity, core body temperature, and blood ethanol concentration, as well as ethanol consumption based on a two-bottle choice test. The authors obtained several baseline measures that allowed for the detection of phenodeviants on these measures as well. To validate this screen, A/J, DBA/2J, and C57BL/6J mouse strains were tested, and previously reported strain differences were found in all phenotypes except ethanol-induced hypothermia. Additionally, two mutant pedigrees were identified: 7TNJ, which exhibited abnormal ethanol-induced locomotor activity, and 112TNR, which exhibited an enhanced ability on the rotarod. These data demonstrate the efficacy of this screen to detect known as well as novel phenotypic differences.

0 Followers
 · 
83 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Alcohol-related responses are under strong genetic regulation. A wealth of alcohol-related data from recombinant inbred (RI) mouse strains enables genetic correlation and mapping of these traits. Previous studies using RI strains have identified numerous chromosomal locations that underlie differential alcohol sensitivity, although the regions identified are typically large. One means to improve power and precision for genetic analysis is to use a larger genetic reference population. The expanded panel of BXD RI mice was used to identify quantitative trait loci (QTLs) associated with sensitivity to locomotor stimulatory and motor incoordinating effects of alcohol. The goals of this study were to determine whether previously reported QTLs were replicated and refined and to determine whether novel QTLs would be identified. Following an i.p. dose of 2.25 g/kg of ethanol (EtOH) or saline control, locomotor activation was assessed using an activity chamber and motor incoordination was assessed using the accelerating rotarod. Male and female BXD mice from over 55 strains were tested. Two treatment paradigms were utilized to evaluate the effects of EtOH versus saline treatment-order. Activity chamber measures showed significant differences in strain, sex, and treatment-order whereas rotarod measures showed significant differences in strain and treatment-order. Significant QTLs for various measures of EtOH-induced locomotor activation were identified on chromosomes 2 and 5 that narrowed QTL regions previously identified from 19 to < 2 Mb. Further, a novel significant QTL for EtOH-induced motor incoordination on chromosome 7 was identified. Using the expanded RI BXD panel, along with a high precision marker map, several novel QTLs were found and several previously identified QTL regions were confirmed and narrowed. The isogenic nature of the population facilitated detection of treatment-order and sex-specific differences. Smaller QTL regions reduced the number of positional candidates thereby increasing the efficiency with which polymorphisms underlying the QTL will be identified.
    Alcoholism Clinical and Experimental Research 01/2013; 37(1):170-83. DOI:10.1111/j.1530-0277.2012.01865.x · 3.31 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A procedure is described for translating high-level knowledge about an application into a neural network architecture that incorporates that knowledge in its synaptic interconnections. The program's design philosophy stresses separation of neural design from network function, a uniform syntax for neurons, inputs, and outputs, and flexibility in modularizing the resulting network. The trainability of neural networks allows the application knowledge to be further fine-tuned for a specific data space. It is shown how the translation rules can allow for the selective training of subnetworks, and an example of a signal recognition algorithm to which this technique can be applied is given
    Acoustics, Speech, and Signal Processing, 1988. ICASSP-88., 1988 International Conference on 01/1989; DOI:10.1109/ICASSP.1989.266979 · 4.63 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A method is proposed in this paper for on line estimation of the ARMA model parameters of a system, whose input is white unmeasurable, stationary, or non-stationary noise. The method is based on the instrumental variable principle for recursive parameter estimation and on fixed-lag smoothing of the equivalent state -space model for deconvolution. The consistency and asymptotic behaviour of this approach are discussed and a simulation study is given, which supports the theoretical results.
    Decision and Control, 1984. The 23rd IEEE Conference on; 01/1985

Preview

Download
1 Download
Available from