Standardizing tests of mouse behavior: Reasons, recommendations, and reality

As more investigators with widely varying backgrounds enter the field of mouse behavioral genetics, there is a growing need to standardize some of the more popular tests because differences between laboratories in the details of behavioral testing and the pretesting environment can contribute to failures to replicate results of genetic experiments. It is argued here that we have sufficient knowledge to warrant a wise choice of a short list of standard strains and even details of apparatus and protocols for several kinds of behavioral tests. Equating the laboratory environment does not appear to be feasible. Instead, we need to learn what kinds of behavioral tests yield the most stable results in different labs and what kinds are most sensitive to the ubiquitous variations among test sites. Methods for making an informed choice of sample size for evaluating interactions between the laboratory environment and genotype are available and should be utilized in standardization trials. New resources for convenient sharing of data will greatly aid in collaborative and comparative studies involving several sites. Like the sequencing of an entire genome, test standardization is something that needs to be done only once if it is done properly, and the work will then benefit the field of behavioral and neural genetics for many years.

[1]  R. Gerlai Gene-targeting studies of mammalian behavior: is it the mutation or the background genotype? , 1996, Trends in Neurosciences.

[2]  Paul E. Sawchenko,et al.  Mice deficient for corticotropin-releasing hormone receptor-2 display anxiety-like behaviour and are hypersensitive to stress , 2000, Nature Genetics.

[3]  R. Rodgers,et al.  Anxiety, defence and the elevated plus-maze , 1997, Neuroscience & Biobehavioral Reviews.

[4]  Jacob Cohen Statistical Power Analysis for the Behavioral Sciences , 1969, The SAGE Encyclopedia of Research Design.

[5]  David P. Wolfer,et al.  Spatial Memory and Learning in Transgenic Mice: Fact or Artifact? , 1998, News in physiological sciences : an international journal of physiology produced jointly by the International Union of Physiological Sciences and the American Physiological Society.

[6]  H. Lipp,et al.  Genetic background changes the pattern of forebrain commissure defects in transgenic mice underexpressing the beta-amyloid-precursor protein. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[7]  Douglas Wahlsten,et al.  Insensitivity of the analysis of variance to heredity-environment interaction , 1990, Behavioral and Brain Sciences.

[8]  M. Poderycki,et al.  Environmental influences on epilepsy gene mapping in EL mice. , 1998, Journal of neurogenetics.

[9]  Wim E Crusio Gene-targeting studies: new methods, old problems , 1996, Trends in Neurosciences.

[10]  M. W. Weir,et al.  Open-Field Behavior in Mice: Evidence for a Major Gene Effect Mediated by the Visual System , 1966, Science.

[11]  E. Russell A history of mouse genetics. , 1985, Annual review of genetics.

[12]  H. Anisman,et al.  Stress-induced disturbances in Morris water-maze performance: Interstrain variability , 1995, Physiology & Behavior.

[13]  J. P. Hegmann,et al.  Genetic analysis of open-field behavior, p. 23-56. In g. Lindzey & d. D. Thiessen (ed.), Contrib. To behavior-genetic , 1970 .

[14]  Lassalle Jm,et al.  Differential effects of the albino gene on behavior according to task, level of inbreeding, and genetic background. , 1981 .

[15]  D. Wahlsten Mice in utero while their mother is lactating suffer higher frequency of deficient corpus callosum. , 1982, Brain research.

[16]  J. Sahel,et al.  The implications of rod-dependent cone survival for basic and clinical research. , 1999, Investigative ophthalmology & visual science.

[17]  S. Maxson Methodological issues in genetic analyses of an agonistic behavior (offense) in male mice , 1992 .

[18]  David Eilam,et al.  Stopping behavior: constraints on exploration in rats (Rattus norvegicus) , 1993, Behavioural Brain Research.

[19]  N. Swerdlow,et al.  Toward Understanding the Biology of a Complex Phenotype: Rat Strain and Substrain Differences in the Sensorimotor Gating-Disruptive Effects of Dopamine Agonists , 2000, The Journal of Neuroscience.

[20]  Jerry Hirsch,et al.  Behavior-Genetic Analysis , 1967 .

[21]  A. C. Collins,et al.  A simple genetic basis for a complex psychological trait in laboratory mice , 1995, Science.

[22]  D. Wahlsten,et al.  Wheel running behavior is impaired by both surgical section and genetic absence of the mouse corpus callosum , 2002, Brain Research Bulletin.

[23]  G Gottlieb,et al.  Normally occurring environmental and behavioral influences on gene activity: from central dogma to probabilistic epigenesis. , 1998, Psychological review.

[24]  D. Wahlsten Sample Size to Detect a Planned Contrast and a One Degree-of-Freedom Interaction Effect , 1991 .

[25]  T. Gasperoni,et al.  A genetic screen for novel behavioral mutations in mice , 2000, Molecular Psychiatry.

[26]  Muriel T. Davisson,et al.  Genetic variation among 129 substrains and its importance for targeted mutagenesis in mice , 1997, Nature Genetics.

[27]  S. Paul,et al.  Mapping Quantitative Trait Loci for Open-Field Behavior in Mice , 1997, Behavior genetics.

[28]  J. Fuller Effects of the albino gene upon behaviour of mice. , 1967, Animal behaviour.

[29]  Douglas Wahlsten,et al.  Techniques for the Genetic Analysis of Brain and Behavior: Focus on the Mouse , 1992 .

[30]  Allan Collins,et al.  Behavioral phenotypes of inbred mouse strains: implications and recommendations for molecular studies , 1997, Psychopharmacology.

[31]  Hanno Würbel,et al.  Behaviour and the standardization fallacy , 2000, Nature Genetics.

[32]  S. Ebihara,et al.  The influence of different light intensities on pineal melatonin content in the retinal degenerate C3H mouse and the normal CBA mouse , 1990, Neuroscience Letters.

[33]  D. Wahlsten,et al.  Hybrid vigour and maternal environment in mice. I. Body and brain growth , 1991, Behavioural Processes.

[34]  K. Henry,et al.  Effects of the albino and dilute loci on mouse behavior. , 1967, Journal of comparative and physiological psychology.

[35]  Janan T. Eppig,et al.  A mouse phenome project , 2000, Mammalian Genome.

[36]  Janan T. Eppig,et al.  Genealogies of mouse inbred strains , 2000, Nature Genetics.

[37]  Wim E Crusio,et al.  Covariations Between Hippocampal Mossy Fibres and Working and Reference Memory in Spatial and Non‐spatial Radial Maze Tasks in Mice , 1993, The European journal of neuroscience.

[38]  J. Schulkin,et al.  Behavioral neuroscience: challenges for the era of molecular biology , 2000, Trends in Neurosciences.

[39]  Susan E. Murray,et al.  Abnormal adaptations to stress and impaired cardiovascular function in mice lacking corticotropin-releasing hormone receptor-2 , 2000, Nature Genetics.

[40]  D. Peeler Shuttlebox performance in BALB/cByJ, C57BL/6ByJ, and CXB recombinant inbred mice: Environmental and genetic determinants and constraints , 1995, Psychobiology.

[41]  Vincent Duquenne,et al.  Neuronal and behavioral differences between Mus musculus domesticus (C57BL/6JBy) and Mus musculus castaneus (CAST/Ei) , 1998, Behavioural Brain Research.

[42]  O. Hermanson,et al.  Deletion of Crhr2 reveals an anxiolytic role for corticotropin-releasing hormone receptor-2 , 2000, Nature Genetics.

[43]  D. Creel Inappropriate use of albino animals as models in research , 1980, Pharmacology Biochemistry and Behavior.

[44]  Maja Bucan,et al.  Behavior and mutagenesis screens: the importance of baseline analysis of inbred strains , 2000, Mammalian Genome.

[45]  Jacqueline N. Crawley,et al.  What's Wrong With My Mouse?: Behavioral Phenotyping of Transgenic and Knockout Mice , 2000 .

[46]  R. Gerlai Chapter 3.1.10 Targeting genes associated with mammalian behavior: past mistakes and future solutions , 1999 .

[47]  M. Nosten-Bertrand,et al.  Additive and Interactive Effects of Genotype and Maternal Environment , 1990 .

[48]  K. Davies,et al.  Testing of SHIRPA, a mouse phenotypic assessment protocol, on Dmdmdx and Dmdmdx3cv dystrophin-deficient mice , 2000, Mammalian Genome.

[49]  Jim J. Hagan,et al.  Use of SHIRPA and discriminant analysis to characterise marked differences in the behavioural phenotype of six inbred mouse strains , 1999, Behavioural Brain Research.

[50]  Douglas Armstrong,et al.  Handbook of Molecular-Genetic Techniques for Brain and Behavior Research , 1999 .

[51]  M. Le Moal,et al.  Abolition and reversal of strain differences in behavioral responses to drugs of abuse after a brief experience. , 2000, Science.

[52]  U. Rudolph,et al.  Resolving differences in GABAA receptor mutant mouse studies , 2000, Nature Neuroscience.

[53]  K. Gärtner,et al.  A third component causing random variability beside environment and genotype. A reason for the limited success of a 30 year long effort to standardize laboratory animals? , 1990, Laboratory animals.

[54]  J. Crabbe,et al.  Genetics of mouse behavior: interactions with laboratory environment. , 1999, Science.

[55]  I. Oshima,et al.  Melatonin Content of the Pineal Gland in Different Mouse Strains , 1989, Journal of pineal research.

[56]  G. Lindzey,et al.  Contributions to behavior-genetic analysis : the mouse as a prototype , 1970 .

[57]  Robert L. Collins,et al.  The effects of early experience on callosal development and functional lateralization in pigmental BALB/c mice , 1992, Behavioural Brain Research.

[58]  S. Hogg A review of the validity and variability of the Elevated Plus-Maze as an animal model of anxiety , 1996, Pharmacology Biochemistry and Behavior.

[59]  Douglas Wahlsten,et al.  Behavioural testing of standard inbred and 5HT1B knockout mice: implications of absent corpus callosum , 2001, Behavioural Brain Research.

[60]  O. Stiedl,et al.  Strain and substrain differences in context- and tone-dependent fear conditioning of inbred mice , 1999, Behavioural Brain Research.

[61]  P M Nolan,et al.  Mouse mutagenesis-systematic studies of mammalian gene function. , 1998, Human molecular genetics.

[62]  D. Wahlsten Single-gene influences on brain and behavior. , 1999, Annual review of psychology.