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The laboratory mouse has emerged as the primary mammalian
system for genomics research and the preeminent surrogate
model system for human disease and normative biology.
Approximately 90 percent of human genes share homology to
genes within the mouse genome. With this similarity to
humans, the mouse model has contributed enormously to
fundamental concepts in cancer biology, immunology,
transplantation biology, genetics, infectious disease, and
many other fields.
A rapidly evolving and increasingly sophisticated
technology has developed for creating mouse models, but
there is a need for making these models available to the
scientific community in order for them to have maximum
impact. In response to the increased number of genetically
modified mice created and used by the biomedical research
community, the NCRR sponsored the development of the Mutant
Mouse Regional Resource Centers (MMRRCs).
The centers are funded under a Cooperative Agreements
mechanism that involves development of animal model
resources with substantial scientific and programmatic
coordination between NCRR and the performing centers. The
MMRRC network comprises an Informatics Coordinating Center
and four regional mutant mouse distribution facilities or
nodes capable of husbandry; cryopreservation; storing and
reconstructing embryos; phenotypic characterization
(structural and behavioral); genetic quality control;
maintenance of a mouse resource database; and distribution
of genetically modified mice to investigators and
institutions throughout the medical research community.
These nodes are located at Harlan Sprague Dawley,
Inc./University of Missouri; Taconic Farms, Inc.; the
University of California, Davis; and the University of
North Carolina at Chapel Hill.
The MMRRC network accepts genetic mouse strains to its
collection, and investigators who have created such models
are encouraged to donate them to the network where they
will then be provided upon request to other investigators
who will use them in research of human health, disease and
treatments.
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The MMRRC nodes have three basic objectives:
- provide a research component to generate new information
that is relevant to the mutant mouse resource;
- serve the needs of investigators in a variety of research
areas where research is sponsored by NIH categorical
institutes; and
- make mutant mice available to investigators on a local,
regional, and national basis.
The Informatics Coordinating Center (ICC) at The Jackson
Laboratory provides an electronic network linking the
MMRRCs by maintaining the database of the resources. The
ICC database is updated continuously and includes live
mouse and cryopreserved germplasm inventory from each MMRRC
node.
The MMRRC Web site provides application forms for
submission of strain candidates to the MMRRC Program,
information on standard supply levels and pricing of MMRRC
strains, and the mechanism to request strains from the
MMRRC nodes. The site can be reached at
www.mmrrc.org.
NCRR anticipates expanding the MMRRC resources in the
future. Further information about grant opportunities may
be obtained from:
Division of Comparative Medicine
National Center for Research Resources
National Institutes of Health
One Democracy Plaza, Room 948
6701 Democracy Boulevard, MSC 4874
Bethesda, Maryland 20892-4874
Telephone: 301-435-0744
FAX: 301-480-3819
e-mail: CMADIR@ncrr.nih.gov
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Harlan Sprague Dawley, Inc.
Laboratory Animal Medicine
298 S. Carroll Road
Indianapolis, IN 46229 |
Principal
Investigator
Robert J. Russell, D.V.M.
317-894-7521; Fax: 317-894-4473 or 1840
E-mail: rjrussell@harlan.com
Additional Contacts, University of Missouri
John K. Critser, Ph.D
800-669-0825; Fax: 573-884-7521
E-mail: critserj@missouri.edu
Lela K. Riley, Ph.D.
800-669-0825; Fax: 573-884-7521
E-mail: rileyl@missouri.edu
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The Harlan/University of Missouri node is focusing on two
areas: Cryobiology research—Projects focus on
improving methods for cryopreservation and banking of mouse
spermatozoa and ovarian tissue. These research efforts are
aimed at increasing the efficacy and efficiency of mouse
genome banking. Health monitoring research—Projects focus on developing novel antemortem techniques for detection of microbial
pathogens. These methods will be especially useful for
monitoring mutant mouse colonies as they avoid the need to
euthanize valuable mutant mice strictly for diagnostic
evaluations.
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273 Hover Avenue
Germantown, NY 12526
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Principal
Investigator
James G. Geistfeld, D.V.M.
518-537-5200 x 227; Fax: 518-537-7287
E-mail: jgei@taconic.com
Additional Contact
Todd Little, Ph.D.
518-537-5200 x 237; Fax: 518-537-7287
E-mail: tlit@taconic.com
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The Taconic node is exploring the value of microarray
technology for mutant phenotyping. A baseline of gene
expression for "normal" mice is being
established. This baseline will allow comparisons with
mutant models. It is anticipated that this will allow
identification of genetic perturbations associated with the
mutation, thus allowing for translation of genotype into
phenotype and function. In addition, behavioral phenotypic
assays are being developed to screen
for behavioral characteristics of mutant models and to
identify modifier regions and genes that affect behavior. A
whole-genome scan is also being performed on several
strains commonly used to create mutants. This information
will be used to plan accelerated backcrossing experiments.
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Center for Comparative Medicine
One Shields Avenue
Davis, CA 95616
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Principal
Investigator
Stephen W. Barthold, D.V.M., Ph.D.
530-752-7913 or 754-9734; Fax: 530-752-7914
E-mail: swbarthold@ucdavis.edu
Additional Contact
Kent Lloyd, Ph.D.
530-752-7913; Fax: 530-752-7914
E-mail: kclloyd@ucdavis.edu
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The node at the University of California, Davis has
developed a research tool called "The Visible
Mouse." This Internet-accessible (ccm@ucdavis.edu/tvmouse)
resource is an educational tool that provides anatomy,
histology, and imaging modalities of the normal mouse, with
navigational tools that allow the user to have access to
the full depth and detail desired.
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Program in Molecular Biology and Biotechnology
221 Fordham Hall, CB 3280
Chapel Hill, NC 27599-3280
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Principal
Investigator
Terry A. Van Dyke, Ph.D.
919-962-2145 or 4449; Fax: 919-962-4296
E-mail: tvdlab@med.unc.edu
Additional Contact
Virginia Godfrey, D.V.M., Ph.D.
919-966-2903; Fax: 919-962-4296
E-mail:
virginia.godfrey@pathology.unc.edu
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The primary objective of the University of North Carolina
node is to offer efficient distribution of breeder pairs
for mutant mouse strains to interested investigators. The
node imports, re-derives, genotypes, maintains and
distributes new mouse strains. It cryopreserves new and
existing mutant strains for archiving and for distribution.
The node also phenotypically characterizes mouse strains
with regard to histopathological, physiological, cell
biological and molecular
abnormalities. Research in mouse models is particularly
strong, with major strengths in the areas of development
and genomics, cardiovascular, and cancer research. Another
major objective is to develop the ability to efficiently
clone mice from somatic cells. This node is also developing
reporter mouse strains that facilitate rapid phenotyping
within particular cell/tissue types.
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600 Main Street
Bar Harbor, ME 04609-1500
URL: www.mmrrc.org
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Principal
Investigator
Larry E. Mobraaten, Ph.D.
207-288-6373; Fax: 207-288-6149
E-mail: lem@jax.org
Additional Contact
Muriel T. Davisson, Ph.D.
207-288-6223; Fax: 207-288-6149
E-mail: mtd@jax.org
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The Informatics Coordinating Center (ICC) at The Jackson
Laboratory provides an electronic network linking the
MMRRCs by maintaining the database of the resources. The ICC
database is updated continuously and includes live mouse and
cryopreserved germplasm inventory from each MMRRC node.
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The Jackson Laboratory
600 Main Street
Bar Harbor, ME 04609-1500
URL: www.jax.org
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Principal
Investigator and Contact
Larry E. Mobraaten, Ph.D.
207-288-6373; Fax: 207-288-6005
E-mail: lem@jax.org
Additional Contacts
Jackson Laboratory Animal Resources
800-422-MICE or 207-288-5845; Fax: 207-288-6150
Carlisle P. Landel, Ph.D.
207-288-6154; Fax: 207-288-6005
E-mail: clandel@jax.org
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To assure the safe preservation of scientifically valuable
strains of laboratory mice by establishing a bank of frozen
mouse embryos and sperm. The program staff is freezing and
storing in liquid nitrogen embryos and sperm from selected
strains of the more than 2,300 inbred and mutant strains of
mice maintained at The Jackson Laboratory. Other objectives
are to reduce the necessary number of different stocks or
size of colonies maintained by conventional breeding
procedures and to retard genetic drift.
Cryopreservation of mouse embryos and spermatozoa.
Reference Services
The repository contains frozen eight-cell mouse embryos and
sperm from genetically defined strains of laboratory mice
that are maintained at The Jackson Laboratory. Embryos and
sperm from more than 2,000 different strains are preserved.
Breeding pairs of mice are made available when such mice
cannot be obtained from conventional breeding sources.
Index Terms
Cryopreservation, germplasm, mouse embryo, spermatozoa.
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The Jackson Laboratory
600 Main Street
Bar Harbor, ME 04609-1500
URL: www.jax.org
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Principal
Investigator
Muriel T. Davisson, Ph.D.
207-288-6223; Fax: 207-288-6149
E-mail: mtd@jax.org
Additional Contacts
Ray Vonder Haar, Ph.D.
207-288-6590
E-mail: rvh@jax.org
Stephen Rockwood
207-288-6437
E-mail: sfr@jax.org
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Research is being conducted on improved methods for
assisted reproduction and speed congenic production. Most
of the targeted mutants arrive on a mixed 129xC57BL/6
genetic background, and as many of these as possible are
backcrossed onto an inbred strain (usually C57BL/6J). In
addition, new mouse models are being created by
intercrossing carriers of specific transgenes and/or
targeted mutations. Simple sequence length polymorphism
(SSLP) DNA markers are being used to characterize and
evaluate differences between inbred strains, substrains,
and embryonic stem cell lines.
The Induced Mutant Resource (IMR) at The Jackson Laboratory
was established in September 1992 in response to concerns
from the scientific community regarding the cost, health,
and distribution of genetically engineered mice
(transgenic, targeted mutant, retroviral insertional
mutant, and chemically induced mutant mice). The function
of the IMR is to select, import, cryopreserve, maintain,
and distribute these important strains of mice to the
research community. To improve their value for research,
the IMR also undertakes genetic development of stocks, such
as transferring mutant genes or transgenes to defined
genetic backgrounds and combining transgenes and/or
targeted mutations to create new mouse models for research.
Over 800 mutant stocks have been accepted by the IMR from 1992 through
February 2000. Current holdings include models for research
on cancer, breast cancer, immunological and inflammatory
diseases, neurological diseases and behavioral,
cardiovascular and heart diseases, developmental, metabolic
and other diseases, reporter (e.g. GFP) and recombinase
(e.g. cre/loxP) strains. About 8 strains a month are being
added to the IMR holdings. A list of all strains may be
obtained from the IMR Web site:
www.jax.org/resources/documents/imr/.
Online submission forms are available at
www.jax.org/resources/documents/imr.
All mice can be ordered by calling The Jackson Laboratory's
Customer Service Department at 1-800-422-MICE or
207-288-5845 or by faxing 207-288-6150. An online,
searchable catalog and online order forms may be found at
http://jaxmice.jax.org/index.shtml. A fee for mice is
charged to partially recover strain maintenance costs and
shipping expenses. For more information about the resource,
contact any of the three investigators listed above or The
Jackson Laboratory's Technical Information Service at
micetech@jax.org.
Updates on strain availablility and other information are
accessible by Internet at
www.jax.org/resources/documents/imr/or
at
http://jaxmice.jax.org/index.shtml.
Index Terms
Cryopreservation, disease models, mouse embryo, mouse
models, mouse sperm, targeted mutations, transgenic mice.
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The Jackson Laboratory
600 Main Street
Bar Harbor, ME 04609-1500
URL: www.jax.org
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Principal
Investigator and Contact
Muriel T. Davisson, Ph.D.
207-288-6223; Fax: 207-288-6149
E-mail: mtd@jax.org
Additional Contacts
Kenneth R. Johnson, Ph.D.
207-288-6228
E-mail: krj@jax.org
Leah Rae Donahue, Ph.D.
207-288-6235
E-mail: lrd@jax.org
Eva M. Eicher, Ph.D.
207-288-6474
E-mail: eme@jax.org
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To discover and characterize new mouse models of human
inherited conditions; to maintain as breeding pairs and
preserve as frozen embryos new and established mouse
mutations and chromosomal aberrations; to develop
genetically suitable stocks of new and established mouse
mutations for use in biomedical research; and to make these
mutant stocks available to interested investigators in the
scientific community.
This resource encourages collaborations with visiting
investigators to screen mutant and wild-derived strains for
specific conditions, symptoms, biochemical or physiological
defects, behavior, or other phenotypes of interest. The
resource provides technical support for users of JAX mice
to answer questions regarding genetics, husbandry, and
characteristics of mutant mice. All mice can be ordered by
calling The Jackson Laboratory's Customer Service
Department at 1-800-422-MICE or 207-288-5845 or by faxing
207-288-6150. An online, searchable catalog and online
order forms may be found at
http://jaxmice.jax.org/index.html. A fee for mice is
charged to partially recover strain maintenance costs and
shipping expenses. For more information about the resource,
contact any of the four investigators listed above. Updates
on strain availability and other information are accessible
by Internet at:
www.jax.org/resources/ documents/mmrhome.html/
The online form
for submission of strains is available at
www.jax.org/resources/
documents/grc/grcspontout.html. Mice
This resource develops and maintains strains of mice with
specific mutant genes in various categories, including
growth and development, reproduction, neurological,
neuromuscular, vision and hearing, skeletal, immunological,
skin and hair, pigmentation, kidney, and enzyme
deficiencies. It also maintains stocks of mice with
chromosomal aberrations including inversions,
translocations, monosomy, and trisomy. In addition, several
wild-derived inbred strains are maintained for linkage
crosses. Details of the mouse strains available from The
Jackson Laboratory are accessible by Internet at
http://jaxmice.jax.org/index.shtml.
Index Terms
Genetic diseases, genetics, mouse, mouse models, mutations.
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The Jackson Laboratory
600 Main Street
Bar Harbor, ME 04609-1500
URL: www.jax.org
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Principal
Investigator and Contact
Muriel T. Davisson, Ph.D.
207-288-6223; Fax: 207-288-6149
E-mail: mtd@jax.org
Additional Contacts
Leah Rae Donahue, Ph.D.
207-288-6235
E-mail: lrd@jax.org
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To make available to the biomedical research community a
collection of special mouse strains for use in gene mapping,
including genetic analysis of complex traits; to enhance
the value of these strains by (1) increasing the number of
DNA (microsatellite and SSLP) markers for which the
recombinant inbred (RI) strain sets have been characterized
to increase the utility of these strains in genetic mapping;
(2) defining more precisely the extent of differential
segments in the congenic strains to enhance their value
as genetic mapping tools; and (3) phenotyping the chromosome
substitution strains (CSS) strains to improve their baseline
characterization, to develop a database of phenotypic
information for the RI, CS and congenic strains in the
resource, to develop graphic maps depicting the limits
of the differential segments in the congenic strains.
The Special Mouse Strains Resource (SMSR) maintains,
cryopreserves and distributes mice from a group of
special strains that are valuable tools for complex
trait analysis and whose use will improve the
efficiency of identifying genes in mouse models of
multigenic human diseases.
Mice
The SMSR includes six RI strain panels, a number of congenic
(CG) strains, and a set of 21 CSS developed by Dr. Joseph
Nadeau at Case Western Reserve University. The RI strains
include: 15 AXB (from an initial cross of an A/J female by
a C57BL/6J male) and 14 reciprocal BXA, 34 BXD
(C57BL/6J x DBA/2J), 12 BXH (C57BL/6J x C3H/HeJ),
13 CXB (BALB/cBy x C57BL/6By), and 14 SWXJ (SWR/J x SJL/Bm)
strains. Each of Dr. Nadeau's CSS carries a single chromosome
(1-19, X or Y) from strain A/J on an otherwise C57BL/6J background.
CG strains maintained by the SMSR include 15 strains congenic for
major histocompatibility complex (H2) haplotypes, 4
congenic at other immunology-related loci, 8 congenic for
obesity-associated quantitative trait loci (QTL) and 8 for
various other loci. These mice can be ordered by calling
The Jackson Laboratory's Customer Service Department at
1-800-422-MICE or 207-288-5845 or by faxing 207-288-6150.
An online, searchable catalog and online order forms may be
found at: http://jaxmice.jax.org/index.html.
A fee for mice is charged to partially recover strain
maintenance costs and shipping expenses. For more information
about the resource, contact either of the investigators
listed above. Updates on strain availability and other
information also are accessible by Internet
at: http://jaxmice.jax.org/index.html.
Index Terms
Complex trait analysis, consomic, gene mapping, genetic diseases,
genetics, mouse, mouse models, mutations, quantitative trait loci,
quantitative trait loci, recombinant inbred.
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University of South Carolina
Department of Biological Sciences
700 Sumter Street Columbia, SC 29208
URL: http://stkctr.biol.sc.edu
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Principal
Investigator
Michael J. Dewey, Ph.D.
803-777-4132; Fax: 803-576-5780
E-mail: dewey@biol.sc.edu
Coprincipal Investigator
Wallace D. Dawson, Ph.D.
803-777-3107; Fax: 803-576-5780
E-mail: wdawson@stkctr.biol.sc.edu
Contact and Colony Manager
Janet Crossland
803-777-3107; Fax: 803-576-5780
E-mail: crosslan@stkctr.biol.sc.edu
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Development of cryopreservation techniques that are
applicable to Peromyscus sperm to enable long-term
preservation of mutant stocks.
The mechanism and genetics of hybrid dysgenesis in
reciprocal hybrids of P. maniculatus and P.
polionotus. Offspring of matings in one direction are
markedly oversized; the reciprocal cross produces
undersized offspring.
Development of an intermediate density map utilizing
PCR-based type 1 (functional genes) and type II
(microsatellite) markers as well as single gene mutants
with coat color or neurological phenotypes; and
interspecific crosses between P. maniculatus and
P. polionotus as well as whole genome radiation
hybrids for linkage determinations. Fruition of the mapping
project will benefit a wide range of investigators
interested in using Peromyscus to study the genetic
basis of speciation, genome imprinting, disease vector
biology, and behavioral and physiological adaptation to
habitat.
The Peromyscus Genetic Stock Center was established
in 1985 and functions to provide a reliable source of
genetically defined and virus-free animals and related
materials to the scientific and eductional communities. The
center currently keeps nine species and more than 27
distinctive mutant and other genetically defined stocks.
Included among the species maintained are P.
californicus, P. leucopus, P. eremicus,
P. aztecus, P. melanophrys as well as two
subspecies each of P. maniculatus and P.
polionotus and three inbred lines of P.
leucopus. Among the mutant stocks are 17 with altered
coat phenotypes, 3 with neurological symptoms, and 6 others
with developmental/physiological effects. One of these is a
line deficient in alcohol dehydrogenase that has been
widely used in studies of alcohol metabolism. The stock
center also supplies biological materials including fresh,
frozen and preserved tissues, molecular probes and
libraries. The center functions as a clearinghouse for
information regarding this genus by sponsoring an Internet
database (PeroBase:
http://wotan.cs.sc.edu/perobase),
and the semi-annual Peromyscus Newsletter. The
center maintains a collection of over 3,000
Peromyscus-related reprints of published articles,
books and journals, photocopies of which are available upon
request. Index Terms
Cryopreservation, deermouse, hantavirus, Lyme disease,
monogamy, mouse genetics, Peromyscus, white-footed
mouse.
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University of Missouri
Comparative Medicine Center and Research Animal Diagnostic
and Investigative Laboratory
Columbia, Missouri 65211
URL: www.radil.missouri.edu/rrrc
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Principal
Investigator and Contact
John K. Critser, Ph.D.
573-884-9469; Fax: 573-884-7521
E-mail: critserj@missouri.edu
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The Rat Resource
and Research Center (RRRC) was established in 2001. The
RRRC is a multi-institutional consortium of investigators
including John K. Critser, Ph.D., and Lela K. Riley, Ph.D.,
at the University of Missouri; Robert J. Russell, D.V.M.,
at Harlan Sprague Dawley, Inc.; and Philip M. Iannaccone,
M.D., Ph.D., at Northwestern University Children's Memorial
Institute for Education and Research.
Research projects are focused in three major areas of
importance to rats as animal models: Development of
efficacious methods for nuclear transfer in the rat;
development of efficient methods for genome resource
banking and strain/stock reconstitution, including ovarian
tissue preservation and transplantation in combination with
artificial insemination with cryopreserved spermatozoa; and
improved methods for health monitoring of rats using
molecular diagnostics and environmental monitoring.
The overall goal is to establish a center for distributing
high quality, well-characterized inbred, hybrid and mutant
rats to investigators. To this end, the RRRC will select
and import rat strains and stocks important to the
biomedical research community; rederive rats to a
pathogen-free state; cryopreserve gametes and embryos;
perform genotyping, phenotyping and infectious disease
monitoring to assure the quality of the rats, and
distribute rats to investigators as live rats,
cryopreserved germplasm or tissues.
Index Terms
Animal models, cryopreservation, genotyping, health
monitoring, nuclear transfer, phenotyping, rats,
reproductive biology.
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Pharmacology and Cell Biophysics
University of Cincinnati College of Medicine
231 Albert Sabin Way
P.O. Box 670575
Cincinnati, OH 45267-0575
URL: www.med.uc.edu/p40resource/
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Principal
Investigator and Contact
Evangelia G. Kranias, Ph.D.
513-558-2377; Fax: 513-558-2269
E-mail: litsa.kranias@uc.edu
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The recent development of phospholamban knockout and
phospholamban overexpression mice has revealed that
phospholamban is a major regulator of basal contractility
in the mammalian cardiac, smooth, and skeletal muscles. The
regulatory effects of phospholamban are mediated through
the Ca2+-ATPase in sarcoplasmic
reticulum (SERCA2), the key enzyme involved in muscle
relaxation. Dephosphorylated phospholamban is an inhibitor
of the sarcoplasmic reticulum
Ca2+-ATPase activity, and
phospholamban relieves this inhibition. The overall
research hypothesis is that alterations in the levels of
the sarcoplasmic reticulum
Ca2+-ATPase or phospholamban, and the
phosphorylated states of phospholamban are associated with
alterations in calcium homeostasis and function of the
muscles. Thus, the long-range research goal of this
resource is to generate animal models with altered
expression in each of these two key
Ca2+-cycling proteins; and altered
expression of phospholamban phosphorylation mutants in
cardiac, smooth, and slow-twitch skeletal muscle. These
mouse models will be made available to the biomedical
community at large to carry out further in-depth studies
and to elucidate the mechanisms underlying intracellular
calcium regulation and physiological responses in health
and disease.
This resource generates and maintains mouse models with
genetic alterations in either phospholamban or the
sarcoplasmic reticulum Ca2+-ATPase in
cardiac, smooth, or slow-twitch skeletal muscle. These
models are initially characterized in the resource and then
they are made available to interested investigators in the
scientific community. A list of all current models may be
obtained from the Sarcoplasmic Reticulum Mutant Mouse
Resource (SR-MMR) Web site.
Index Terms
Ca2+-ATPase, calcium, genetics,
knockout mouse, muscle, phospholamban, sarcoplasmic
reticulum, transgenic mice.
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