In search of a better mouse test

Wahłsten, Douglas; Rustay, Nathan R.; Metten, Pamela; Crabbe, John C.

doi:10.1016/s0166-2236(03)00033-x

Cited by 138 publications

(96 citation statements)

References 49 publications

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“…Citalopram had less anti-immobility effect in 129/Sv mice than in C57BL/6J mice, and no dose dependency was observed. This may be partly explained by the fact that this strain performs poorly in several tests involving locomotor activity and/or exploration, such as open field (present study) or Y maze and Barnes maze (Wahlsten et al, 2003). However, differences in locomotor activity can hardly explain the different effects of citalopram in the FST in the other strains.…”

Section: Discussionmentioning

confidence: 66%

“…However, Lucki et al (2001) showed that fluoxetine reduced immobility time in DBA/2J and BALB/c mice, had no effect in C57BL/6J, and increased immobility in 129/SvemJ mice. Although this apparently argues against a role for allelic differences in TPH-2 in the effect of SSRIs, the genotype-environment interaction may cause differences in behavioral phenotype across laboratories (Crabbe et al, 1999;Wahlsten et al, 2003;Kafkafi et al, 2005). Differences in the SSRIs, substrain, and procedures used may also contribute.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Genotype-Dependent Activity of Tryptophan Hydroxylase-2 Determines the Response to Citalopram in a Mouse Model of Depression

Cervo¹,

Canetta²,

Calcagno³

et al. 2005

J. Neurosci.

129

132

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Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Genotype-Dependent Activity of Tryptophan Hydroxylase-2 Determines the Response to Citalopram in a Mouse Model of Depression

Cervo¹,

Canetta²,

Calcagno³

et al. 2005

J. Neurosci.

129

132

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“…Perhaps one reason for this is that laboratories are often comparing behavior by using somewhat different apparatus and͞or testing protocols. For example, the elevated plus maze, one of the more common tests of anxiety in rodents, differs frequently across laboratories in lighting conditions and in the wall height of the open, more anxiogenic portion of the maze, which affects alley selection of the subjects (21). Many different tests of learning and memory are used, often as if they were interchangeable, but genetic influence is likely to depend on specific parameters for these tests, too.…”

Section: Discussionmentioning

confidence: 99%

Assessment of genetic susceptibility to ethanol intoxication in mice

Rustay

Wahłsten

Crabbe

2003

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

102

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Increased use of gene manipulation in mice (e.g., targeted or random mutagenesis) has been accompanied by increased reliance on a very few rapid and simple behavioral assays, each of which aspires to model a human behavioral domain. Yet, each assay comprises multiple traits, influenced by multiple genetic factors. Motor incoordination (ataxia), a common characteristic of many neurological disorders, may reflect disordered balance, muscle strength, proprioception, and͞or patterned gait. Impaired motor performance can confound interpretation of behavioral assays of learning and memory, exploration, motivation, and sensory competence. The rotarod is one of the most commonly used tests to measure coordination in mice. We show here that exactly how the rotarod test is performed can markedly alter the apparent patterns of genetic influence both in undrugged performance and sensitivity to ethanol intoxication. However, when tested with well chosen parameters, the accelerating rotarod test showed very high inter-and intralaboratory reliability. Depending on test conditions, ethanol can either disrupt or enhance performance in some strains. Genetic contribution to performance on the accelerating versus the fixed-speed rotarod assay can be completely dissociated under some test conditions, and multiple test parameters are needed to assess the range of genetic influence adequately.T he loss of motor coordination (ataxia) is a common characteristic of many neurological disorders and a frequent endpoint for studies of drug intoxication. Therefore, behavioral assays that model ataxia are of great importance to researchers who are interested in learning more about the mechanisms of drug action and disease. One of the most commonly used tests of motor incoordination is the rotarod (1-4), which has two variants: the accelerating rotarod (ARR) and the fixed-speed rotarod (FSRR). Studies of inbred strains (5-8), selected lines (9), and transgenic animals (10-12) have shown that rotarod performance is highly influenced by genetic background in mice. Genetically distinct mice often differ in their undrugged ability to perform, and differ in their sensitivities to ethanol and other drugs on the task.Although the rotarod is widely used in biomedical research, there is little consensus on the ideal parameters and test schedules to produce optimal results. We have recently completed studies in genetically heterogeneous mice examining the influence of different rod diameters, rotation rate, and training regimens on rotarod performance, as well as their effects on sensitivity to ethanol intoxication. We obtained some expected results (e.g., training on the ARR improved performance, and performance was influenced by acceleration rate). More surprisingly, we found that higher acceleration rates suppressed sensitivity to ethanol intoxication. We also found that rod diameter did not markedly affect performance, provided that the diameter was large enough to prevent passive rotation on the rod (13).Many researchers appear to design behavioral ...

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“…On Wednesday there were ten acquisition trials on the accelerating rotarod [14,15], followed by rotarod trials before and after a saline injection on Thursday and before and after an ethanol injection (2 mg/kg) on Friday. The next week there was 1 day of pretraining and then 4 days of training on a hidden platform water escape task [20]. Finally, food consumption and body size were monitored over a weekend and then mice were deprived of food for 24 h and given a test of food eating on Tuesday.…”

Section: Behavioral Testingmentioning

confidence: 99%

“…The 40 strains are divided into priority groups A, B, C, and D with ten strains each [20], chosen to represent a wide diversity of mouse genotypes. At the outset of the MPP in 1999, the highest priority group A included the little known strain BTBR T / + tf/tf, but that strain was later moved by MPP staff to the lowest priority group D. Our work with behavioral tests in two laboratories began in 2000 with the original group A, and we found some interesting behavioral differences in the BTBR mice, especially their superior performance on the accelerating rotarod [14,15].…”

Section: Introductionmentioning

confidence: 99%

Survey of 21 inbred mouse strains in two laboratories reveals that BTBR T/+ tf/tf has severely reduced hippocampal commissure and absent corpus callosum

2003

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A morphometric survey of brain size and forebrain commissures of 21 inbred mouse strains from the Jackson Laboratory was done with animals tested in two laboratories as part of the Mouse Phenome Project. Strain BTBR T / + tf/tf was found to have 100% total absence of the corpus callosum as well as severe reduction of the hippocampal commissure in almost every animal, the most severe commissure defect observed to date in any commercially available mouse strain. The strain 129S1/SvImJ had a milder defect with incomplete penetrance.Crosses of BTBR mice with inbred strains BALB/cWah1, 129P1/ReJ, and the recombinant strain 9XCA/Wah having a severe commissure defect supported a two-locus model of the genetic defect in these strains. Brain size varied greatly among strains but for any one strain was almost identical in mice housed for 5 weeks in the two laboratories. Sex differences in brain weight and forebrain commissure sizes were not statistically significant. Theme: Disorders of the nervous system Topic: Genetic models

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In search of a better mouse test

Cited by 138 publications

References 49 publications

Genotype-Dependent Activity of Tryptophan Hydroxylase-2 Determines the Response to Citalopram in a Mouse Model of Depression

Genotype-Dependent Activity of Tryptophan Hydroxylase-2 Determines the Response to Citalopram in a Mouse Model of Depression

Assessment of genetic susceptibility to ethanol intoxication in mice

Survey of 21 inbred mouse strains in two laboratories reveals that BTBR T/+ tf/tf has severely reduced hippocampal commissure and absent corpus callosum

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