Systematic, standardized and comprehensive neurological phenotyping of inbred mice strains in the German Mouse Clinic

Neurological and psychiatric disorders are among the most common and most serious health problems in developed countries. Transgenic mouse models mimicking human neurological diseases have provided new insights into development and function of the nervous system. One of the prominent goals of the German National Genome Research Network is the understanding of the in vivo function of single genes and the pathophysiological and clinical consequences of respective mutations. The German Mouse Clinic (GMC) offers a high-throughput primary screen of genetically modified mouse models as well as an in-depth analysis in secondary and tertiary screens covering various fields of mouse physiology. Here we describe the phenotyping methods of the Neurological Screen in the GMC, exemplified in the four inbred mouse lines C57BL/6J, C3HeB/FeJ, BALB/cByJ, and 129S2/SvPas. For our primary screen, we generated "standard operating procedures" that were validated between different laboratories. The phenotyping of inbred strains already showed significant differences in various parameters, thus being a prerequisite for the examination of mutant mouse lines.

[1]  R. Pabst,et al.  Behavioral phenotyping of mice in pharmacological and toxicological research. , 2003, Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie.

[2]  A. Kalueff,et al.  Hair barbering in mice: Implications for neurobehavioural research , 2006, Behavioural Processes.

[3]  M. Gratacós,et al.  Neurobehavioral development of two mouse lines commonly used in transgenic studies , 2002, Pharmacology Biochemistry and Behavior.

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

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

[6]  M. Bogue,et al.  Mouse Phenome Project: understanding human biology through mouse genetics and genomics. , 2003, Journal of applied physiology.

[7]  W. Stühmer,et al.  The structure and function of Na+ channels , 1992, Current Opinion in Neurobiology.

[8]  E. Fisher,et al.  SHIRPA, a protocol for behavioral assessment: validation for longitudinal study of neurological dysfunction in mice , 2001, Neuroscience Letters.

[9]  F. V. D. Staay,et al.  Behavioural phenotyping of mouse mutants , 2001, Behavioural Brain Research.

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

[11]  John M. Hancock,et al.  BIOINFORMATICS APPLICATIONS NOTE Databases and ontologies EMPReSS: European Mouse Phenotyping Resource for Standardized Screens , 2005 .

[12]  K. Miczek,et al.  Aggressive behavioral phenotypes in mice , 2001, Behavioural Brain Research.

[13]  G. Kusek,et al.  Differences among eight inbred strains of mice in motor ability and motor learning on a rotorod , 2003, Genes, brain, and behavior.

[14]  Robert Lalonde,et al.  Rotorod sensorimotor learning in cerebellar mutant mice , 1995, Neuroscience Research.

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

[16]  T. Robbins,et al.  Neurobehavioural mechanisms of reward and motivation , 1996, Current Opinion in Neurobiology.

[17]  L. Ryan,et al.  Subthalamic nucleus lesions induce deficits as well as benefits in the hemiparkinsonian rat , 1999, The European journal of neuroscience.

[18]  Nicholas W Wood,et al.  Mouse models for neurological disease , 2002, The Lancet Neurology.

[19]  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.

[20]  Jan H. van Bemmel,et al.  Progress in Computer-Assisted Function Analysis , 1988 .

[21]  Jacqueline N. Crawley,et al.  A Proposed Test Battery and Constellations of Specific Behavioral Paradigms to Investigate the Behavioral Phenotypes of Transgenic and Knockout Mice , 1997, Hormones and Behavior.

[22]  I. Whishaw,et al.  The Dalila effect: C57BL6 mice barber whiskers by plucking , 2000, Behavioural Brain Research.

[23]  S. Dunnett,et al.  The Placement of a Striatal Ibotenic Acid Lesion Affects Skilled Forelimb Use and the Direction of Drug-Induced Rotation , 1996, Brain Research Bulletin.

[24]  Werner Müller,et al.  Introducing the German Mouse Clinic: open access platform for standardized phenotyping , 2005, Nature Methods.

[25]  Stephen B. Dunnett,et al.  Characterization of Progressive Motor Deficits in Mice Transgenic for the Human Huntington’s Disease Mutation , 1999, The Journal of Neuroscience.

[26]  E. Fisher,et al.  Behavioral and functional analysis of mouse phenotype: SHIRPA, a proposed protocol for comprehensive phenotype assessment , 1997, Mammalian Genome.

[27]  S. Dunnett,et al.  Behavioural profiles of inbred mouse strains used as transgenic backgrounds. II: cognitive tests , 2004, Genes, brain, and behavior.

[28]  V. Bogo,et al.  Comparison of accelerod and rotarod sensitivity in detecting ethanol- and acrylamide-induced performance decrement in rats: review of experimental considerations of rotating rod systems. , 1981, Neurotoxicology.

[29]  S. Dunnett,et al.  The staircase test of skilled reaching in mice , 2001, Brain Research Bulletin.

[30]  T. Roderick,et al.  FVB/N: an inbred mouse strain preferable for transgenic analyses. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[31]  Stephen C. Grubb,et al.  The Mouse Phenome Project , 2004, Genetica.

[32]  S. Pellis,et al.  Analysis of limb use by control rats and unilateral DA-depleted rats in the Montoya staircase test: movements, impairments and compensatory strategies , 1997, Behavioural Brain Research.

[33]  D. Bates,et al.  Mixed-Effects Models in S and S-PLUS , 2001 .

[34]  F. Lestienne,et al.  Sensorimotor Learning in Three Cerebellar Mutant Mice , 1996, Neurobiology of Learning and Memory.

[35]  D. Abrous,et al.  Dopamine-rich grafts in the neostriatum and/or nucleus accumbens: Effects on drug-induced behaviours and skilled paw-reaching , 1993, Neuroscience.

[36]  H. Zoghbi,et al.  Modelling brain diseases in mice: the challenges of design and analysis , 2003, Nature Reviews Genetics.

[37]  S. Dunnett,et al.  The “staircase test”: a measure of independent forelimb reaching and grasping abilities in rats , 1991, Journal of Neuroscience Methods.

[38]  Hiroshi Masuya,et al.  Implementation of the modified-SHIRPA protocol for screening of dominant phenotypes in a large-scale ENU mutagenesis program , 2005, Mammalian Genome.

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

[40]  R. Wise,et al.  The neurobiology of addiction , 2019, Annals of the New York Academy of Sciences.

[41]  P. Winn,et al.  Excitotoxic lesions of the pedunculopontine tegmental nucleus of the rat. II. Examination of eating and drinking, rotation, and reaching and grasping following unilateral ibotenate or quinolinate lesions , 1992, Brain Research.

[42]  J. Crawley.  Behavioral phenotyping of transgenic and knockout mice: experimental design and evaluation of general health, sensory functions, motor abilities, and specific behavioral tests 1 Published on the World Wide Web on 2 December 1998. 1 , 1999, Brain Research.

[43]  J. Beckmann,et al.  Human-mouse differences in the embryonic expression patterns of developmental control genes and disease genes. , 2000, Human molecular genetics.

[44]  S. Kõks,et al.  Strain and gender differences in the behavior of mouse lines commonly used in transgenic studies , 2001, Physiology & Behavior.

[45]  S. Irwin,et al.  Comprehensive observational assessment: Ia. A systematic, quantitative procedure for assessing the behavioral and physiologic state of the mouse , 1968, Psychopharmacologia.

[46]  Gary A. Churchill,et al.  A collaborative database of inbred mouse strain characteristics , 2004, Bioinform..

[47]  A. V. Anagnostopoulos,et al.  Transgenic and knockout databases Behavioral profiles of mouse mutants , 2001, Physiology & Behavior.

[48]  M. Staufenbiel,et al.  Neurobehavioral characterization of APP23 transgenic mice with the SHIRPA primary screen , 2005, Behavioural Brain Research.

[49]  A. Mackay-Sim,et al.  Behavioural characterization of Vitamin D receptor knockout mice , 2005, Behavioural Brain Research.

[50]  Victor H. Denenberg,et al.  A behavioral and neuroanatomical assessment of an inbred substrain of 129 mice with behavioral comparisons to C57BL/6J mice , 1999, Brain Research.