Online Issues

Journal Vol 47(2)

Internet Resources for Phenotyping Engineered Rodents

Brad Bolon

Brad Bolon, D.V.M., M.S., Ph.D., Diplomate, A.C.V.P. and A.B.T., is the founder of GEMpath Inc. (“Genetically Engineered Mouse pathology”), an experimental pathology consulting practice based in Cedar City, Utah.

Abstract

Genetically engineered mice (GEM) and rats (GER) have emerged as the main mammalian models for investigating normal (physiological, or “health”) and abnormal (pathological, or “disease”) mechanisms. Regardless of the genetic manipulation, novel GEM and GER must undergo meticulous genotypic and phenotypic analyses before it is possible to predict the significance of the engineered gene with respect to health and disease, especially when the desire is to extrapolate the findings to humans. Numerous websites have been generated to give researchers additional tools to facilitate genotyping and phenotyping. This list of many extant sites with descriptions of their basic features provides a starting point for new and established scientists faced with the need to characterize a new GEM or GER model.

Key Words: functional genomics; genotype; internet; mouse; phenogenomics; phenotype; rat; website

Since the early 1990s, genetically engineered mice (GEM¹) and rats (GER¹) have evolved from a novelty to a mainstay in modern academic and industrial research programs tasked with investigating normal (physiological, or “health”) and abnormal (pathological, or “disease”) mechanisms in mammals. A large portion of this interest is founded on the premise that the activity of a modified gene in an engineered rodent can be used to predict the function of a faulty human gene that bears a similar genetic anomaly (Sharp et al. 2000). The truth of this assertion has been proven by the demonstration that pharmacological effects in humans of the 100 top-selling drugs correlate well with the anticipated outcome observed in GEM lacking the molecular targets for these agents (Zambrowicz and Sands 2003). Thus, the collective experience in this field indicates that GEM and GER add great value both to basic research programs designed to discover fundamental principles of mammalian physiology and to applied research efforts to define and correct molecular aberrations responsible for many human diseases (Bolon 2004).

Several different technological means are currently used to produce GEM and GER models (Bolon et al. 2000; Charreau et al. 1996; Rudolph and Moehler 1999; Shastry 1998; Wei 1997). However, regardless of the genetic manipulation, new engineered lines must proceed through comprehensive genotypic (Faerman and Shani 1998; Franco et al. 2001; Shibata et al. 2002) and phenotypic (Bilbo and Nelson 2001; Brayton et al. 2001; Bronson 2001; Car and Eng 2001; Crawley 2000; Murray 2002; Relyea et al. 2000; Rossant and McKerlie 2001; Ullman-Culleré and Foltz 1999) evaluations before it is possible to appraise the impact of the modified gene. Current practice in such phenogenomic research programs is to use a predefined battery of screening tests to examine the genotype and phenotype of GEM and GER (Brayton et al. 2001; Moser 2000; Rogers et al. 1997), modified as necessary to employ more targeted procedures that will highlight new phenotypes in organ systems of particular interest for each researcher (Brockway et al. 1998; Hartley et al. 2002; Herschman et al. 2000; Lindon et al. 2004; Louie et al. 2000). A composite understanding of the phenotype in the engineered animal can then be used to guide subsequent mechanistic experiments.

An auxiliary resource that augments the information gained by direct genotypic and phenotypic analyses is the growing list of Internet sites that cater to scientists engaged in genetic engineering. Since the mid 1990s, a horde of websites has been launched to assist genotyping and phenotyping efforts and to begin bringing the power of bioinformatics to the discipline of mouse biology. The recent literature contains a growing number of articles that catalog these sources. However, most of these compilations offer only brief lists (Anagnostopoulos et al. 2001; Boschert 1996; Donnelly 2004; Rossant and McKerlie 2001; Zeiss 2002) or are not easily accessible to the general public (Fiette 2005), and few contain enough commentary to judge the potential utility of a site quickly (Donnelly 2004; Zeiss 2002). Furthermore, many links in older collections are not maintained and eventually become inactive.

In the following review of resources, I categorize many websites and briefly describe the most useful ones available at the time of this writing. I emphasize those that are inclusive and lasting portals to other on-line resources, and I highlight materials that I believe will aid novice researchers to find relevant resources in highly specialized fields that terrify many scientists (e.g., embryology, neural function). My intent is that the given sites and their myriad links will serve as a useful starting point for researchers preparing to phenotype novel GEM and GER lines. Obviously, though, new websites in this field arise and old links become obsolete almost daily, so the current document represents only a first taste to whet the appetite for further Internet exploration in this arena.

BASIC FEATURES OF RODENT BIOLOGY

ANATOMY AND HISTOLOGY

Anatomy of the Laboratory Mouse (Jackson Laboratory)
http://www.informatics.jax.org/cookbook/
A collection of well-labeled diagrams from many but not all systems. The index is particularly useful because the key words are followed by hyperlinks to the relevant figures.

High Resolution Mouse Brain Atlas
http://www.hms.harvard.edu/research/brain/atlas.html#
An atlas of coronal sections from a young adult mouse, labeled to highlight neurons and myelin. A “Labels” button calls forth a larger, well-annotated view.

Histology Atlas—Deltabase
http://www.deltagen.com/target/histologyatlas/HistologyAtlas.html
A database showing normal microscopic anatomy of mouse organs and tissues. Images are arranged by system. Each image is simply annotated to show basic anatomical features.

Histology Atlas—University of Illinois
http://www.med.uiuc.edu/histo/small/atlas/index.htm
An archive showing normal microscopic anatomy of organs and tissues from multiple species. The database may be searched by organ (using “Slides”) as well as by cell type or subcellular organelle (via “Objects”).

Mouse Brain Atlas
http://www.mbl.org/atlas170/atlas170_frame.html
An atlas of coronal sections from a young adult male C57BL/6J mouse. The “Brain Atlas” link at the bottom of the home page leads to a list of brain atlases (many still under construction) for other mouse strains, at different ages, in coronal and horizontal orientations.

Mouse Models of Human Cancers Consortium (MMHCC) Image Archive
http://imagearchive.compmed.ucdavis.edu
A series of minimally annotated images from selected normal tissues from humans and mice.

Neurophenotyping (University of Tennessee)
http://neurophenotyping.utmem.edu/index2%20.html
A site showing mouse brain sections labeled with multiple different stains to emphasize different cell populations.

Virtual Slide Box (University of Iowa)
http://www.path.uiowa.edu/virtualslidebox
An archive showing microscopic anatomy of normal and diseased organs and tissues from multiple species. The database may be searched by species, organ, and/or diagnosis. A “Comparative Search” tool allows side-by-side comparison of two images simultaneously.

Visible Mouse
http://ccm.ucdavis.edu/tvmouse
An archive of gross and microscopic anatomy as well as functional imaging of normal and diseased organs of wild-type and engineered mice. Many pages are still under construction, and most make heavy use of large multimedia files.

PHYSIOLOGY

Centre for Modelling Human Diseases
http://www.cmhd.ca/enu_mutagenesis/physiology_stats/physiology_stats.html
A modest list of physiological data for selected mouse organ systems.

Inbred Strain Characteristics (Jackson Laboratory)
http://www.informatics.jax.org/external/festing/mouse/STRAINS.shtml
An alphabetical portal with links to extensive biological characterizations of hundreds of inbred mouse strains. This site is a superb means of obtaining a rapid and thorough overview of strain-specific anatomy and physiology.

EMBRYOLOGY

Comparative Placentation
http://medicine.ucsd.edu/cpa/indxfs.html
An impressive site with text and images to compare placental structure among many species. The most simple means for accessing the mouse and rat data is to use the “Index” button and then scroll to the bottom to find the “Rodentia” section.

DevTox
http://www.devtox.org/
A collection of definitions and in some cases photographs depicting various developmental anomalies in mice, rats, and rabbits.

Edinburgh Mouse Atlas Project (EMAP)
http://genex.hgu.mrc.ac.uk/intro.html
A three-dimensional interactive atlas of mouse development based on extant texts describing mouse developmental anatomy and physiology (Kaufman 1992; Kaufman and Bard 1999; Theiler 1989). The database covers most of gestation and includes both reconstructed images and line drawings of various Theiler stages in conjunction with interpretive text.

Edinburgh Mouse Atlas Gene Expression (EMAGE)
http://genex.hgu.mrc.ac.uk/intro.html
A color-coded array of in situ gene expression over time, imposed on the images of embryos and extraembryonic membranes in the Edinburgh Mouse Atlas Project (EMAP) atlas of mouse development. Data may be evaluated for specific organs and tissues in two and three dimensions.

Embryo Images Online
http://www.med.unc.edu/embryo_images/unit-welcome/welcome_htms/akgs.htm
A three-dimensional atlas of mouse embryogenesis composed of high-resolution scanning electron micrographs segregated by organ system. New pages under development promise to address normal fetal development and the anatomical basis of birth defects.

GENETICS

Ensembl
http://www.ensembl.org/index.html
A clearinghouse for evaluating, annotating, and comparing genomes among eukaryotic species, including multiple mouse and rat lineages as well as other vertebrate species.

Mouse Genetics (Jackson Laboratory)
http://www.informatics.jax.org/silver/
A Web-adapted version of Lee Silver's excellent but difficult to obtain Mouse Genetics, arranged by chapter.

Mouse Genome
http://www.nature.com/nature/mousegenome
A series of research papers from Nature that fully detail the initial sequencing of the mouse genome.

Mouse Genome Informatics (Jackson Laboratory)
http://www.informatics.jax.org
A portal for integrated access to genetic and genomic data for many mouse strains. Links provide access to searchable databases that match mutations (both engineered and spontaneous) to phenotypes, describe gene maps and markers, and allow comparison of genomic information among species.

Rat Genome Database
http://rgd.mcw.edu/
A comprehensive portal for mouse and rat genetic and genomic information.

HUSBANDRY

Mouse Breeding Suggestions (Transgenic Animal Web [University of Michigan])
http://www.med.umich.edu/tamc/breed.html
A brief compilation of basic husbandry and breeding tips related to mice.

GENOTYPING

METHODS

Protocol Online
http://www.protocol-online.org/prot/Genetics_Genomics/index.html
A core site with links to many procedures for genetic, genotyping, and gene expression assays.

RESOURCES

Cancer Genome Anatomy Project (CGAP)
http://cgap.nci.nih.gov
The home page for a program dedicated to dissecting the genetic events that promote cancer initiation and progression. The searchable database contains information from human and mouse genomic libraries.

Mammalian Gene Collection (MGC)
http://mgc.nci.nih.gov/
A searchable database of full-length cDNAs from several mammalian species, including mice and rats. The archive contains several thousand genes per species but has yet to be completed.

Mouse Genome Resources (MGR)
http://www.ncbi.nlm.nih.gov/genome/guide/mouse
A portal for numerous searchable databases of trans-species genomic information.

PHENOTYPING

GENERAL

Centre for Modelling Human Diseases
http://www.cmhd.ca/enu_mutagenesis/physiology_assays.html
A portal for many techniques for functional phenotyping of induced mouse mutants.

Eumorphia European Mouse Phenotyping Resource of Standardised Screens (EMPReSS)
http://www.eumorphia.org/EMPReSS/servlet/EMPReSS.Frameset
A systematic series of standard operating procedures (for both functional and structural assays) suitable for primary phenotypic screening of novel mutant mice.

Institute for Laboratory Animal Research (ILAR)
http://dels.nas.edu/ilar_n/ilarhome/index.shtml
A general resource for scientific and policy discussions regarding laboratory animals in biomedical research. The free online archive of the ILAR Journal includes several issues devoted to mouse models, such as the recent volume devoted to “Mouse Models of Human Disease” (http://dels.nas.edu/ilar_n/ilarjournal/43_2/).

Phenome Database (Jackson Laboratory)
http://www.jax.org/phenome
The home page for an extensive collection of mouse physiological data that can be searched by strain, organ system, or measured parameter. Links to protocols for acquiring such data are also provided.

Protocol Online
http://www.protocol-online.org/
A core site with links to many procedures for animal-based investigation of human diseases, including histology, pathology, and surgical methods.

SHIRPA Protocol for Phenotypic Assessment
http://www.mgu.har.mrc.ac.uk/facilities/mutagenesis/mutabase/shirpa_summary.html
A text and tabular description of a comprehensive functional and structural phenotyping protocol for mice.

BEHAVIOR

METHODS

Key-Obs
http://www.key-obs.com/tests.htm
An index of routine assays offered by a firm geared to behavioral assessment of mice and rats. Details of the test methodology are not given because the company functions as a fee-for-service enterprise.

NeuroInvestigations
http://www.neuroinvestigations.com/models/m_mousep.htm
An index of standard behavioral tests used in mouse behavioral assessment. Again, details of the test methodology are not given because the firm functions as a fee-for-service source of neural phenotyping expertise.

Neuromice
http://www.tnmouse.org/neuromutagenesis/behavioral.html
An extensive collection of behavioral tests with simple protocols to investigate multiple aspects of mouse neural function.

Psychogenics
http://www.psychogenics.com/sv-index-of-tests.shtml
An index of standard behavioral tests describing potential measures of each assay, in many cases including graphs showing representative data. Again, procedural details are not given because the company offers fee-for-service neural phenotyping.

CLINICAL

METHODS

Charles River Laboratories
http://www.criver.com/research_models_and_services/
Entry page for a list of clinical and surgical procedures for evaluating organ and system function and structure in rodents.

Jackson Laboratory Phenotyping Services
http://jaxmice.jax.org/services/phenotyping.html
A comprehensive portal to resources for mouse physiological phenotyping, including assays relevant to cardiovascular, metabolic, nervous, and pulmonary function.

Mouse Phenotyping Laboratory (University of Cincinnati)
http://gri.uc.edu/PAGES/mou_phe.html
Contact page for service dedicated to physiological measurements of cardiac, metabolic, and renal function.

Mouse Specifics
http://www.mousespecifics.com/products/
Home page for a firm engaged in noninvasive analysis of cardiac and neural function in mice and rats.

NetVet Rodents
http://netvet.wustl.edu/rodents.htm
An excellent portal containing myriad links to websites describing genotypic and phenotypic analysis of rodents, including mice and rats. Some links are no longer active.

PATHOLOGY

EXPERTISE

The institutions listed below have achieved lasting recognition as sites that provide high-quality genotyping and phenotyping services on a contract basis. Academic entities usually accept only small projects from external collaborators, whereas the industrial concerns can perform larger projects. Important Note: I strongly, strongly, STRONGLY urge researchers who intend to employ a contract phenotyping facility to consult the prospective service provider before the rodents are scheduled to be analyzed. Ignore this recommendation and you invite an acute case of GIGO (“garbage in, garbage out”) syndrome that will slow or even halt the productivity of your mouse phenogenomic efforts.

ACADEMIA

German Mouse Clinic
http://www0.gsf.de/ieg/gmc/index.html

Institut Clinique de la Souris (University of Strasbourg [France])
http://www-mci.u-strasbg.fr/ao.html

Johns Hopkins University Rodent Phenotyping Center
http://www.hopkinsmedicine.org/comparativemedicine/phenocenter/

Ohio State University Mouse Phenotyping Shared Resource
http://www.vet.ohio-state.edu/255.htm

University of California-Davis Mutant Mouse Pathology Laboratory
http://tgmouse.compmed.ucdavis.edu/HistoLab/

University of Michigan Unit for Laboratory Animal Medicine
http://www.ulam.umich.edu/services/pathcons.htm

University of Missouri–Columbia Research Animal Diagnostic Laboratory (RADIL)
http://www.radil.missouri.edu/info/diagtesting/services/pathology.asp

Yale University Mouse Research Pathology
http://mrp.yale.edu/index.html

INDUSTRY

Charles River Laboratories
http://criver.com/research_models_and_services/transgenic_services/tgsphenotyping.html

Frimorfo
http://www.frimorfo.com

Jackson Laboratory Phenotyping Services
http://jaxmice.jax.org/services/phenotyping.html
A comprehensive portal to resources for mouse anatomical phenotyping.

Taconic
http://www.taconic.com/RAS/phenotyping.htm

GOVERNMENT

NCI [National Cancer Institute] Pathology & Histotechnology Laboratory
http://web.ncifcrf.gov/rtp/lasp/phl/

GENERAL METHODS

Pathmax
http://www.pathmax.com/main.html
A comprehensive compilation of links to thousands of sites for medical and veterinary pathology.

Pathology and Biology of Genetically Engineered Mice
http://www.niaid.nih.gov/dir/services/animalcare/VetPathology/Genetically-Engineered%20Mice.html
A series of links to mouse phenotyping resources on the Web.

Pathology Useful Links (Institute for Cancer Genetics, Columbia University)
http://icg.cpmc.columbia.edu/cattoretti/Protocol/Links.html
A clearinghouse for rodent pathology resources on the Web.

NECROPSY

Guide to Necropsy of the Mouse (EUropean Late Effects Project [EULEP])
http://www.eulep.org/Necropsy_of_the_Mouse/index_2004.php
A good necropsy protocol for evaluating adult mice. The large photographs make this an excellent resource for self-study.

Mouse Virtual Necropsy
http://tvmouse.compmed.ucdavis.edu/virtualNecropsy/
An interactive necropsy protocol for evaluating adult mice. The delineation of specific organs to examine along with the precise approaches needed to isolate them (using paired “before” and “after” photographs) makes this another superb site for self-study.

Virtual Mouse Necropsy
http://www.niaid.nih.gov/dir/services/animalcare/Mousenecropsy/necropsy.html
Another detailed necropsy protocol for evaluating adult mice. The schematic figures are well labeled.

TISSUE PROCESSING

Registry Nomenclature Information System (RENI)
http://www.item.fraunhofer.de/reni/trimming/TR_F.htm
A well-written and -illustrated guide for sampling organs and tissues of adult rats. The home page (http://www.item.fraunhofer.de/reni/index.htm) provides many links to additional pages describing mouse organs.

HISTOLOGICAL STAINING TECHNIQUES

Histological Staining techniques (University of Bristol, UK)
http://www.bris.ac.uk/Depts/PathAndMicro/CPL/histmeth.htm
An alphabetized and searchable compilation of detailed recipes for many traditional histological stains.

Histology Procedure Manuals (University of Utah)
http://www.medlib.med.utah.edu/WebPath/HISTHTML/MANUALS/MANUALS.html
A list of recipes for many fixatives, stock solutions, and conventional histological stains, along with standard safety procedures for histology laboratory.

IMMUNOHISTOCHEMISTRY

Antibodies Applied to Mouse Tissue
http://tumor.informatics.jax.org/html/antibodies.html
An alphabetical listing of antibodies (available in both Excel and HTML formats) describing staining conditions, results, and suggested control tissues for dozens of antibodies.

Anti-mouse Primary Antibodies (Columbia University)
http://icg.cpmc.columbia.edu/cattoretti/Protocol/Mouse_IHC/Antibodies_for_mouse_IHC.html
A list of antibodies to detect several dozen epitopes on hematopoietic, immune, or neoplastic cells in mice.

Immunohistochemistry (Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences [NIEHS])
http://dir.niehs.nih.gov/dirlep/immuno
A searchable database containing detailed protocols and numerous images for detecting dozens of antigens in rodent and human tissues.

Immunoportal
http://www.immunoportal.com
A clearinghouse for online protocols for immunohistochemistry and in situ hybridization. Features include large image galleries of successful staining runs, searchable databases of reagent vendors, and forums for trouble shooting with like-minded investigators.

Murine Immunohistochemistry Database (National Cancer Institute [NCI])
http://web.ncifcrf.gov/rtp/lasp/phl/immuno
A searchable database that provides optimized technical details for detecting several hundred antigens in mouse tissues.

IN SITU HYBRIDIZATION

Immunoportal
http://www.immunoportal.com

IMAGING

Biophotonic Platforms
www.xenogen.com
The corporate website for a leading manufacturer of real-time noninvasive devices for evaluating gene expression in rodents.

Center for In Vivo Microscopy (Duke University)
http://www.civm.duhs.duke.edu/
A research center with a willingness to undertake collaborative research in functional cardiovascular imaging and high-resolution in vivo microscopy.

Center for Molecular and Genomic Imaging (CMGI)
http://cmgi.bme.ucdavis.edu/
A fee-for-service resource for performing computerized tomography, positron emission tomography, optical (bioluminescent and fluorescent), and ultrasound scanning procedures on rodents.

VisualSonics
http://www.visualsonics.com/
Home page for a company that produces high-resolution, noninvasive imaging systems for rodent research.

PATHOLOGY FINDINGS

Histology Atlas of the Mouse Mammary Gland (National Institutes of Health)
http://mammary.nih.gov/atlas and http://mammary.nih.gov/tools/
A well-organized site that demonstrates whole mount and microscopic structure in normal and abnormal tissue from wild-type and mutant mice, with links to companion platforms to compare pathology in human and mouse lesions.

Mammalian Phenotype Browser (Jackson Laboratory)
http://www.informatics.jax.org/searches/MP_form.shtml
A searchable, hierarchical, alphabetical listing of phenotypes in numerous tissues cross-referenced to relevant genetic details and published descriptions.

Mouse Models with Immunological Phenotypes (Harvard University)
http://immunology.tch.harvard.edu/Knockouts
A searchable database for published descriptions of mouse mutants that bear gene-related defects in immune function. Genes may be explored by name, organ, phenotype, or key words.

Mouse Tumor Biology Database
http://tumor.informatics.jax.org/mtbwi/index.do
A searchable database containing details regarding the biology of induced and inherited neoplasms in many mouse strains. An allied database of tumor images can be explored by organ system, diagnosis, or antigen expression. Links are provided to many other websites related to cancer biology.

Neurogenetics Online (University of Texas Health Science Center)
http://www.nervenet.org/
A growing high-resolution brain atlas of histological and magnetic resonance images as well as genomic databases in dozens of mouse lines. The home page has a link to the Mouse Brain Library (http://www.mbl.org/).

Pathbase
http://eulep.anat.cam.ac.uk/
A searchable archive showing gross and microscopic images derived from mutant mice. Photographs can be retrieved using many different parameters, including accession numbers that are linked to other mutant mouse databases.

Standardized System of Nomenclature and Diagnostic Criteria Guidelines (SSNDC)
https://www3.afip.org/cgi-bin/bookstore.cgi#TOXIC
A site from the US Armed Forces Institute of Pathology for purchasing monographs detailing anatomical descriptions of common lesions in humans, rats, and mice. (The rodent SSNDC offerings are accessed via the “Guides of Toxicologic Pathology” link.)

COMPILATIONS

DATABASES

Cre Transgenic Database
http://nagy.mshri.on.ca/PubLinks/indexmain.html
A searchable database (still under construction) containing details on several hundred lines of conditional transgenic mice.

Database of Gene Knockouts
http://bioscience.org/knockout/knochome.htm
An alphabetical compilation of several dozen lines of knockout mice, which provides an outline of the major phenotypic features. An alternative name is the World Directory of Knockout Mice (http://www.bioscience .org/knockout/alphabet.htm).

German Gene Trap Consortium
http://genetrap.gsf.de
A specialty reference library for insertional mutations generated in mouse embryonic stem cells using gene trap techniques. The site contains a searchable database of gene sequences and relevant literature as well as gene trap protocols.

International Gene Trap Consortium (IGTC)
www.genetrap.org
Home page for a searchable database of all publicly available cell lines containing insertional mutations generated by gene trap methods.

Mouse Models of Human Cancers Consortium (MMHCC)
http://emice.nci.nih.gov/emice
A portal for mouse models of human neoplasia for multiple organ systems. Links to publications and online tutorials are a prominent feature of this site.

Mouse Models of Human Cancers Consortium (MMHCC) Image Archive
http://imagearchive.compmed.ucdavis.edu
A collection of images from human and mouse neoplasms from selected sites, sorted by organ system.

Mouse Tumor Biology Database
http://tumor.informatics.jax.org/mtbwi/index.do

Tetmouse Base
http://www.zmg.uni-mainz.de/tetmouse
A collection of general and tissue-specific conditional mutant mice generated using tetracycline-regulated elements. Tables include links to references that describe the phenotype as well as contact information for the principal scientists.

Trans-NIH Mouse Initiative
http://www.nih.gov/science/mouse
A central resource for coordinating mouse genomic research.

Whole Mouse Catalog
http://www.rodentia.com/wmc/index.html
This excellent portal, the successor to the Mouse and Rat Research home page, serves as a clearinghouse for myriad websites that cater to rodent researchers. Some links are inactive.

DISCUSSION GROUPS

Comparative Medicine (COMPMED)
listserv@listserv.aalas.org
A broad-based discussion of numerous topics in laboratory animal medicine, including many references to biology of normal and engineered rodents.

Embryo Mail
http://embryomail.anri.barc.usda.gov/
A moderated site for discussing any topic in mammalian embryology.

Histonet
http://www.histosearch.com/histonet/
An interactive forum for addressing technical issues in histology.

Mouse Genetics Informatics (Jackson Laboratory)
http://www.informatics.jax.org/mgihome/lists/lists.shtml
A pair of lists for scientists interested in mouse genetic research and mouse phenotyping.

Mutant Mouse Pathology ListServ
http://www.niaid.nih.gov/dir/services/animalcare/VetPathology/Genetically-Engineered%20Mice.html
A roundtable venue for discussing problems generated by efforts to phenotype new mutant mouse lines.

Transgenic List
http://mailman.ic.ac.uk/mailman/listinfo/transgenic-list
A discussion group for topics in genetic engineering of mammals, especially rodents.

RODENTS

NOMENCLATURE

Mouse Nomenclature Home Page (Jackson Laboratory)
http://www.informatics.jax.org/mgihome/nomen/index.shtml
Authoritative source of official names for mouse genes, alleles, mutations, and strains based on rules established by the International Committee on Standardized Genetic Nomenclature for Mice.

SOURCES

ACADEMIA/PRIVATE FOUNDATION

Australian Phenomics Facility
http://www.apf.edu.au/resources/
A large-scale chemical mutagenesis program designed to detect immunological phenotypes in mice.

Canadian Mouse Mutant Resource (CMMR)
http://www.cmmr.ca/index.html
An archive of cryopreserved embryonic stem cells, gametes, embryos, or tissue DNA as well as preserved tissue samples from mutant mouse models.

European Mutant Mouse Archive (EMMA)
http://www.emma.rm.cnr.it/
A nonprofit collaborative storehouse for the collection, maintenance (by cryopreservation), and distribution of mutant mouse strains.

Federation of International Mouse Resources (FIMRe)
http://www.informatics.jax.org/imsr/ifmr.html
This worldwide consortium of mouse resource centers is a multisite archive of cryopreserved embryos, gametes, embryonic stem cell lines, and live breeding stock.

Induced Mutant Resource (Jackson Laboratory)
http://www.jax.org/imr/index.html
A clearinghouse for the collection, maintenance, and distribution of mice engineered to carry a transgene or null mutation (by either gene targeting or chemical mutagenesis).

International Mouse Strain Resource
http://www.informatics.jax.org/imsr/index.jsp
A searchable online database of mouse strains and stocks (including inbred as well as induced and spontaneous mutants) available worldwide.

Jackson Laboratory Mice
http://www.jax.org/resources/mouse_resources.html
A comprehensive menu of strains, genotypes, gene names, and controls for many inbred, hybrid, congenic, consomic, and genetically engineered mutant mice.

Mammalian Genetics Resource (MGR)
http://www.mgu.har.mrc.ac.uk/facilities/stocklist/search.html

Mutant Mouse Regional Resource Centers (MMRRC)
http://www.mmrrc.org/
A multisite repository for cryopreserved mutant mouse lines with proven phenotypes. The consortium is funded by the National Institutes of Health National Center for Research Resources.

COMMERCIAL

Charles River Laboratories
http://www.criver.com/research_models_and_services/research_models/ index.html
A list of rodent inbred, outbred, hybrid, and immunodeficient mouse and rat strains and stocks.

Harlan
http://www.harlan.com/mmrrc.htm
An extensive list of mice and rats, including inbred, outbred, hybrid, congenic, and mutant models. This company is a member (in collaboration with the University of Missouri-Columbia) of the Mutant Mouse Regional Resource Centers Consortium.

Lexicon Genetics—Omnibank
http://www.lexicon-genetics.com/discovery/omnibank.htm
A portal to a cryopreserved library of mutant embryonic stem cells that can be acquired to reconstitute thousands of knockout mouse lines.

Taconic
http://www.taconic.com/anmodels/animlmod.htm
A long catalog of mice and rats, including inbred, outbred, hybrid, congenic, and mutant (induced and spontaneous) models. This firm is a member (in combination with the State University of New York-Albany) of the Mutant Mouse Regional Resource Centers Consortium.

GOVERNMENT

Japan Mouse Strain Resources
http://shigen.lab.nig.ac.jp/mouse/jmsr/strains.jsp

Oak Ridge National Laboratory Mutant Mouse Database
http://www.bio.ornl.gov/mouse/
A portal for mouse stocks with transmissible mutations induced by chemical or radiation treatment of gametes.

RIKEN BioResource Center (Japan)
http://www.brc.riken.jp/lab/animal/en/ or http://www.gsc.riken.go.jp/Mouse/
A not-for-profit resource center engaged in archiving (by cryopreservation) and analyzing (genotypic and phenotypic) inbred and mutant mice.

Acknowledgment

I thank Reviewer 2 for the thorough effort given to vetting this manuscript, and particularly for the addition of several relevant websites on rodent phenotyping. I sincerely appreciate the improvement to this review.

Abbreviations used in this article: GEM, genetically engineered mouse/mice; GER, genetically engineered rat/rats.

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