ABSTRACT
Mice altered by transgenesis or gene targeting ("knockouts") have increasingly been employed as alternative effective tools in elucidating the genetic basis of neurophysiology and behavior. Standardization of specific behavioral paradigms and phenotyping strategies will ensure that these behavioral mouse mutants offer robust models for evaluating the efficacy of novel therapeutics in the treatment of hereditary neurological disorders. The Induced Mutant Resource (IMR) at The Jackson Laboratory (Bar Harbor, Maine, USA) imports, cryopreserves, develops, maintains, and distributes to the research community biomedically valuable stocks of transgenic and targeted mutant mice. Information on behavioral and neurological strains-including a phenotypic synopsis, husbandry requirements, strain availability, and genetic typing protocols-is available through the IMR database (http://www.jax.org/resources/documents/imr/). A current catalog of available strains is readily accessible via the JAX Mice Web site at http://jaxmice.jax.org/index.shtml. In addition, The Jackson Laboratory is now home to TBASE (http://tbase.jax.org/), a comprehensive, community database whose primary focus is on mouse knockouts. TBASE accommodates an exhaustive bibliographical resource for transgenic and knockout mice and provides a detailed phenotypic characterization of numerous behavioral knockouts that is primarily extracted from the literature. Concerted efforts to merge the two resources into a new, schematically reformed database are underway.
Subject(s)
Behavior, Animal/physiology , Mice, Knockout/genetics , Mice, Transgenic/genetics , Phenotype , Animals , Brain/physiology , Catalogs as Topic , Databases, Genetic , Genetics , Internet , MiceABSTRACT
Genetically engineered strains of mice, modified by transgenesis or gene targeting ("knockouts") are being generated at an impressive rate and used, among other areas, as premiere research tools in deciphering the genetic basis of behavior. As behavioral phenotyping strategies continue to evolve, characterization of these "designer" mice will provide models to evaluate the efficacy of new pharmacological and gene therapy treatments in human hereditary diseases. Reported behavioral profiles include aberrant social, reproductive, and parental behaviors, learning and memory deficits, feeding disorders, aggression, anxiety-related behaviors, pain/analgesia, and altered responses to antidepressants, antipsychotics, ethanol, and psychostimulant drugs of abuse. The Induced Mutant Resource (IMR) at The Jackson Laboratory (TJL, Bar Harbor, ME, USA) imports, cryopreserves, develops, maintains, and distributes biomedically important stocks of transgenic and targeted mutant mice to the research community. Information on neurological/behavioral strains--including behavioral performance, husbandry requirements, strain availability, and genetic typing protocols--is provided through the IMR database (http://www.jax.org/resources/documents/imr/). A catalog of available strains is readily accessible via the JAX Mice website at http://jaxmice.jax.org/index.shtml. In addition, TJL is now host to TBASE (http://tbase.jax.org/), a comprehensive, public-domain database with primary emphasis on mouse knockouts. TBASE contains an exhaustive list of knockout-related citations and provides an extensive phenotypic characterization of numerous behavioral mutants that is extracted directly from the literature. Present efforts to merge the two resources into a novel, schematically enhanced database, provisionally named Transgenic and Targeted Mutation Database (TTMD), will be briefly discussed.
Subject(s)
Behavior, Animal/physiology , Databases as Topic , Mice, Knockout/genetics , Mice, Neurologic Mutants/genetics , Mice, Transgenic/genetics , Animals , Genetics, Behavioral , Internet , Mice , PhenotypeABSTRACT
'It's a Knockout!' provides an update of some of the latest mouse knockouts in TBASE (http://www.jax.org/tbase/ and Ref. 1). The column provides a concise phenotypic profile of novel mutants and renders their complete characterization directly accessible to Web users, via unique and unchanging accession numbers (TBASE identities). Where possible, interesting knockouts will be grouped according to gene families, application or phenotypic similarities.
Subject(s)
Databases, Factual , Internet , Mice, Knockout/genetics , Animals , Female , Male , Mice , Mutation , PhenotypeSubject(s)
Immediate-Early Proteins , Mice, Knockout , Potassium Channels, Inwardly Rectifying , RNA-Binding Proteins , Animals , DNA-Binding Proteins/genetics , Early Growth Response Protein 1 , Fragile X Mental Retardation Protein , Homeodomain Proteins/genetics , Mice , Nerve Tissue Proteins/genetics , Nitric Oxide Synthase/genetics , Nitric Oxide Synthase Type II , Nitric Oxide Synthase Type III , Potassium Channels/genetics , Receptors, Atrial Natriuretic Factor/genetics , Receptors, Thyroid Hormone/genetics , Transcription Factors/genetics , Transglutaminases/genetics , Vimentin/genetics , alpha-Glucosidases/geneticsSubject(s)
DNA-Binding Proteins , Genetic Diseases, Inborn/genetics , Mice, Knockout , Nuclear Proteins , Protein-Tyrosine Kinases , Animals , CD18 Antigens/genetics , Dermatitis/genetics , Desmin/deficiency , Desmin/genetics , Female , Hepatocyte Nuclear Factor 1 , Hepatocyte Nuclear Factor 1-alpha , Hepatocyte Nuclear Factor 1-beta , Humans , Infertility, Male/genetics , Male , Mice , Receptor, Fibroblast Growth Factor, Type 3 , Receptors, Fibroblast Growth Factor/genetics , Transcription Factors/deficiency , Transcription Factors/geneticsSubject(s)
Computer Communication Networks , Mice, Knockout , Animals , Database Management Systems , MiceABSTRACT
Overexpression of human-specific c-neu proto-oncogene transmembrane tyrosine kinase receptor protein (p185) is an index of cell transformation and of poor patient survival in several malignancies. The authors studied this protein in low- and high-grade human malignant astrocytomas before and after xenografting into aspiration pockets in rat cortex. Human-specific p185c-neu-positive cells were found in tumor specimens from all grades of astrocytoma. Significantly fewer p185c-neu-positive cells were observed in the low-grade versus the high-grade astrocytomas examined (p < 0.05). Human specific p185c-neu-positive cells were also positive for the human major histocompatibility complex, human leukocyte antigen (HLA)-DR, as well as glial fibrillary acidic protein and S-100 protein. Fresh suspensions of tumor tissue were prelabeled with the plant lectin Phaseolus vulgaris leukoagglutinin and xenografted into pockets in rat cortex. A class of human p185c-neu-positive cells found in tissue samples from all grades of astrocytoma migrated in the rat brain along parallel and intersecting nerve fibre bundles and basement membrane-lined surfaces. Migrated p185c-neu-positive cells were also positive for HLA-DR, Phaseolus vulgaris leukoagglutinin, glial fibrillary acidic protein, and S-100 protein, suggesting that they were in fact human astrocytoma cells. Simultaneous expression of human p185c-neu, HLA-DR, and glial fibrillary acidic protein was observed in a class of human malignant astrocytoma cells in both tumor tissue and xenografted cells that migrated into rat brain. These molecules are signature proteins for the study of the spread of human malignant astrocytomas in an animal model, and indicate that transformed human malignant astrocytoma cells can migrate within the parenchyma of the central nervous system and could play a role in the development of multifocal tumors.
