Experimenter effects on behavioral test scores of eight inbred mouse strains under the influence of ethanol.

Eight standard inbred mouse strains were evaluated for ethanol effects on a refined battery of behavioral tests in a study that was originally designed to assess the influence of rat odors in the colony on mouse behaviors. As part of the design of the study, two experimenters conducted the tests, and the study was carefully balanced so that equal numbers of mice in all groups and times of day were tested by each experimenter. A defect in airflow in the facility compromised the odor manipulation, and in fact the different odor exposure groups did not differ in their behaviors.

A contemporary view of genes and behavior: complex systems and interactions.

Several large-scale searches for genes that influence complex human traits, such as intelligence and personality, in the normal range of variation have failed to identify even one gene that makes a significant difference. All previously published claims for genetic influences of this kind now appear to have been false positives. For more serious psychiatric and medical disorders such as schizophrenia and autism, several genes have been found where a rare mutation contributes to abnormal behavior, but in many instances they are de novo mutations not obtained from a parent.

The hunt for gene effects pertinent to behavioral traits and psychiatric disorders: from mouse to human.

The field of behavioral genetics was reviewed in the classic 1960 text by Fuller and Thompson. Since then, there has been remarkable progress in the genetic analysis of animal behavior. Many molecular genetic methods in common use today were not even anticipated in 1960.

Hippocampal commissure defects in crosses of four inbred mouse strains with absent corpus callosum.

It is known that four common inbred mouse strains show defects of the forebrain commissures. The BALB/cJ strain has a low frequency of abnormally small corpus callosum, whereas the 129 strains have many animals with deficient corpus callosum. The I/LnJ and BTBR T+ tf/J strains never have a corpus callosum, whereas half of I/LnJ and almost all BTBR show severely reduced size of the hippocampal commissure.

Reversed light-dark cycle and cage enrichment effects on ethanol-induced deficits in motor coordination assessed in inbred mouse strains with a compact battery of refined tests.

The laboratory environment existing outside the test situation itself can have a substantial influence on results of some behavioral tests with mice, and the extent of these influences sometimes depends on genotype. For alcohol research, the principal issue is whether genotype-related ethanol effects will themselves be altered by common variations in the lab environment or instead will be essentially the same across a wide range of lab environments. Data from 20 inbred strains were used to reduce an original battery of seven tests of alcohol intoxication to a compact battery of four tests: the balance beam and grip strength with a 1.

The precision of video and photocell tracking systems and the elimination of tracking errors with infrared backlighting.

Automated tracking offers a number of advantages over both manual and photocell tracking methodologies, including increased reliability, validity, and flexibility of application. Despite the advantages that video offers, our experience has been that video systems cannot track a mouse consistently when its coat color is in low contrast with the background. Furthermore, the local lab lighting can influence how well results are quantified.

Digit ratio (2Dratio4D) differences between 20 strains of inbred mice.

The second to fourth digit ratio (2Dratio4D) is sexually differentiated in a variety of species, including humans, rats, birds, and lizards. In humans, this ratio tends to be lower in males than in females. Lower digit ratios are believed to indicate increased prenatal testosterone exposure, and are associated with more masculinized behavior across a range of traits.

Calibration of rotational acceleration for the rotarod test of rodent motor coordination.

The latency of mice and rats to fall from the accelerating rotarod can differ markedly between laboratories using the same brand of rod as well as between studies using different kinds of rods. These discrepancies can arise from different rod diameters, surface textures, test protocols, or laboratory environmental factors beyond the test itself, but it is also possible that the actual acceleration rates of the different rods do not correspond to the nominal rates set on the devices. This paper describes a simple method to measure acceleration rate of the rotarod and to set the rate to a desired value for any brand of rod.

Overview of mouse assays of ethanol intoxication.

There are many behavioral assays to assess sensitivity to ethanol intoxication in mice. Most are simple to implement, and are sensitive to a particular dose range of ethanol. Most reflect genetic influences, and each test appears to reflect the contribution of a relatively distinct collection of genes.

Impaired fear memory, altered object memory and modified hippocampal synaptic plasticity in split-brain mice.

The hippocampus is critical for memory formation. However, the contributions of the hippocampal commissure (HC) and the corpus callosum (CC) are less clear. To elucidate the role of the forebrain commissures in learning and memory, we performed a behavioural and electrophysiological characterization of an inbred mouse strain that displays agenesis of the CC and congenitally reduced HC (BTBR T+ tf/J; 'BTBR').

Stability of inbred mouse strain differences in behavior and brain size between laboratories and across decades.

If we conduct the same experiment in two laboratories or repeat a classical study many years later, will we obtain the same results? Recent research with mice in neural and behavioral genetics yielded different results in different laboratories for certain phenotypes, and these findings suggested to some researchers that behavior may be too unstable for fine-scale genetic analysis. Here we expand the range of data on this question to additional laboratories and phenotypes, and, for the first time in this field, we formally compare recent data with experiments conducted 30-50 years ago. For ethanol preference and locomotor activity, strain differences have been highly stable over a period of 40-50 years, and most strain correlations are in the range of r = 0.

Localization of two new X-linked quantitative trait loci controlling corpus callosum size in the mouse.

Corpus callosum (CC) size is a complex trait, characterized by a gradation of values within a normal range, as well as abnormalities that include a small or totally absent CC. Among inbred mouse strains with defects of the CC, BTBR T(+)tf/J (BTBR) mice have the most extreme phenotype; all animals show total absence of the CC and severe reduction of the hippocampal commissure (HC). In contrast, the BALB/cByJ (BALB) strain has a low frequency of small CC and consistently normal HC.

Effects of genetic and procedural variation on measurement of alcohol sensitivity in mouse inbred strains.

Mice from eight inbred strains were studied for their acute sensitivity to ethanol as indexed by the degree of hypothermia (HT), indexed as the reduction from pre-injection baseline of their body temperature. Two weeks later, mice were tested for their loss of righting reflex (LRR) after a higher dose of ethanol. The LRR was tested using the "classical" method of watching for recovery in animals placed on their backs in a V-shaped trough and recording duration of LRR.

Recombinant inbreeding in mice reveals thresholds in embryonic corpus callosum development.

The inbred strains BALB/cWah1 and 129P1/ReJ both show incomplete penetrance for absent corpus callosum (CC); about 14% of adult mice have no CC at all. Their F(1) hybrid offspring are normal, which proves that the strains differ at two or more loci pertinent to absent CC. Twenty-three recombinant inbred lines were bred from the F(2) cross of BALB/c and 129, and several of these expressed a novel and severe phenotype after only three or four generations of inbreeding - total absence of the CC and severe reduction of the hippocampal commissure (HC) in every adult animal.

Different rankings of inbred mouse strains on the Morris maze and a refined 4-arm water escape task.

The submerged platform or Morris water escape task is widely used to study genetic variation in spatial learning and memory, but interpretation is sometimes difficult because of wall hugging, jumping off the platform, floating or non-spatial swim strategies. We modified the task by introducing four wide arms into the circular tank and adding features that reduced, eliminated, or compensated for several competing behaviors. Three versions of the 4-arm task were evaluated in detail, and the third version yielded good results for six of eight inbred strains.

Digit ratio (2D:4D) and behavioral differences between inbred mouse strains.

Digit ratio (2D:4D) is a trait, which is sexually differentiated in a variety of species. In humans, males typically have shorter second digits (2Ds) (index fingers) compared to fourth digits (4Ds) (ring fingers) whereas females' fingers are more equal in length. Smaller, more masculine, digit ratios are thought to be associated with higher prenatal testosterone levels, greater sensitivity to prenatal androgens or both.

An analysis of the genetics of alcohol intoxication in inbred mice.

We compared the behaviors of eight inbred mouse strains across 18 variables, using 11 behavioral assays, and gave ethanol (EtOH) as an intoxicant. Genetic influences on behavior and sensitivity to EtOH were pronounced, but strain sensitivities were generally only modestly correlated across tasks. Certain well-correlated clusters of responses suggested that some genes affect similar neurobiological substrates.

Observer-rated ataxia: rating scales for assessment of genetic differences in ethanol-induced intoxication in mice.

Identification of genetic and physiological mechanisms underlying a drug's or mutation's effects on motor performance could be aided by the existence of a simple observation-based rating scale of ataxia for mice. Rating scales were developed to assess ataxia after ethanol (2.75, 3.

Strain differences in three measures of ethanol intoxication in mice: the screen, dowel and grip strength tests.

Mice from 8 to 21 inbred strains were tested for sensitivity to ethanol intoxication using a range of doses and three different measures: the screen test, the dowel test and a test of grip strength. Strains differed under nearly all conditions. For the dowel test, two dowel widths were employed, and mice were tested immediately or 30 min after ethanol.

A rating scale for wildness and ease of handling laboratory mice: results for 21 inbred strains tested in two laboratories.

Rating scales for difficulty in capturing and holding mice were devised that proved to be easy to use and highly sensitive to differences among mouse strains on the A and B priority lists of the Mouse Phenome Project. The simplicity of the scales makes it feasible to rate wildness during behavioral test sessions without adding much to testing time or distracting the technician from the principal task at hand. Overall wildness and placidity ratings obtained by combining capture and hold ratings provide a good impression of the difficulties encountered while working with lab mice in the course of complex experiments.

Influence of task parameters on rotarod performance and sensitivity to ethanol in mice.

Motor performance in mice can be assessed with multiple apparatus and protocols. Use of the rotarod (a.k.

Genotypic differences in ethanol sensitivity in two tests of motor incoordination.

Motor incoordination is frequently used as a behavioral index of intoxication by drugs that depress the central nervous system. Two tasks that have been used to assay incoordination in mice, the balance beam and the grid test, were evaluated to optimize aspects of apparatus and testing procedures for studying genetic differences. Mice of eight inbred strains were given one of several doses of ethanol or saline and tested for intoxication.