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Strain Name:
MSN/GammMmmh
Stock Number:
036809-MU
Citation ID:
RRID:MMRRC_036809-MU
Other Names:
MaD1, Mania model mice

Strain Information

Genetic Alterations
Various forms of selective breeding along with genetic drift led to the current strong phenotype for mania.
Genotype Determination
Phenotype

This strain shows several traits including elevated cage activity, decreased sleep, elevated swimming, and elevated sexual behavior that are consistent with mania, a component of BPD. This is a multigene mouse model for mania, a component of bipolar disorder (BPD). The most prominent phenotype is the spontaneous, extremely elevated cage hyperactivity for both males and females. Females have higher activity than males. This activity is twice that of control outbred mice, and it has been repeatedly documented in different generations and studies. A number of genes identified, including P2rx7, show dysregulated expression in these mice and are also dysregulated in individuals with BPD. Chromosome hotspots were found with a high number of dysregulated genes and these hotspots correspond to chromosome regions in humans (via shared synteny) that are strongly linked with BPD. Studies suggest the mice do not cycle between manic and depressive poles, so the mice, likely, just represent a manic pole. At the time of archiving, the donor was conducting an exome study, hoping to identify specific gene changes in the mice.

MeSH Terms
  • Aggression/physiology
  • Animals
  • Body Weight/physiology
  • Female
  • Gryllidae
  • Individuality
  • Male
  • Maternal Behavior/physiology
  • Mice
  • Mice, Inbred ICR
  • Motor Activity/physiology
  • Organ Size/physiology
  • Predatory Behavior/physiology
  • Testis/anatomy & histology
  • Testis/physiology
  • Testosterone/blood
  • Behavior, Animal
  • Brain/metabolism
  • Dopamine/metabolism
  • Maternal Behavior
  • Models, Animal
  • Models, Biological
  • Mothers
  • Neurons/metabolism
  • Nucleus Accumbens/metabolism
  • Pregnancy
  • Risk Factors
  • Signal Transduction
  • Antimanic Agents/therapeutic use
  • Benzodiazepines/therapeutic use
  • Bipolar Disorder/drug therapy
  • Bipolar Disorder/physiopathology
  • Body Weight/drug effects
  • Dark Adaptation/drug effects
  • Dark Adaptation/physiology
  • Disease Models, Animal
  • Exploratory Behavior/drug effects
  • Lithium Chloride/therapeutic use
  • Sexual Behavior, Animal/drug effects
  • Sleep/drug effects
  • Swimming/psychology
  • Behavior, Animal/physiology
  • Bipolar Disorder/genetics
  • Chromatin/metabolism
  • Gene Regulatory Networks/genetics
  • Genetic Predisposition to Disease
  • Genome, Human/genetics
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Reproducibility of Results
  • Reverse Transcriptase Polymerase Chain Reaction
Strain GQC Summary
Gene Specific Genotyping:

To request gene-specific and other genotyping services for a strain, please contact the distribution MMRRC Center for more information.

Background Genetic Quality:

The MMRRC has developed a Genetic Quality Control pipeline using the MiniMUGA array to provide additional information to identify and validate genetic backgrounds of MMRRC strains. For more information on whether genetic background data is available, please contact MMRRC_GeneticQC@med.unc.edu. Note: that MiniMUGA genetic background data is not available on all strains, but can be ordered if desired.

Suggested Control Mice
Littermates of all relevant genotypes.
Submitter
Stephen Gammie, Ph.D., University of Wisconsin.
Primary Reference

Gammie SC, Hasen NS, Rhodes JS, Girard I, Garland T Jr. Predatory aggression, but not maternal or intermale aggression, is associated with high voluntary wheel-running behavior in mice. Horm Behav. 2003 Sep;44(3):209-21. (Medline PMID: 14609543)

Gammie SC, Edelmann MN, Mandel-Brehm C, D'Anna KL, Auger AP, Stevenson SA. Altered dopamine signaling in naturally occurring maternal neglect. PLoS One. 2008 Apr 9;3(4):e1974. (Medline PMID: 18398484)

Scotti MA, Lee G, Stevenson SA, Ostromecki AM, Wied TJ, Kula DJ, Gessay GM, Gammie SC. Behavioral and pharmacological assessment of a potential new mouse model for mania. Physiol Behav. 2011 Jun 1;103(3-4):376-83. Epub 2011 Mar 22. (Medline PMID: 21397618)

Saul MC, Gessay GM, Gammie SC. A new mouse model for mania shares genetic correlates with human bipolar disorder. PLoS One. 2012;7(6):e38128. Epub 2012 Jun 4. (Medline PMID: 22675514)

Strain Development
The mice have a long history. They were first derived from outbred Hsd:ICR mice (in the 1990s) and were one of four mouse lines that were selected for high wheel-running by Dr. Ted Garland when he was still at the University of Wisconsin-Madison. The donor's lab identified this line as having unusually high levels of maternal protective behavior and one could think of this as manic mothers who are overly protective. This was published in 2003 (PMID:14609543). The line, at that point, was unique and the initial phenotype had likely emerged due to genetic drift because no other selected or control lines showed this high protective trait. The donor used selective breeding to maintain high protectiveness. Further gene selection and genetic drift would have occurred. In the following years, the donor stopped selective breeding, replacing it with randomly breeding. The donor then noticed a number of features of this line over time and began to evaluate this line as a possible model for mania, as published in 2011 (PMID:21397618) describing the mania-like traits and response to common anti-BPD treatments, lithium and olanzapine. At the time of archiving, the line was likely about 98% inbred.

This strain was developed from Hsd:ICR mice by approximately 35 generations of selective, high, voluntary wheel-running originated from one of the four mouse lines created by Dr. Theodore Garland. This strain has been maintained on Hsd:ICR mice for about 15 generations. Dr. Stephen Gammie characterized behavioral, pharmacological, and genetic traits by conducting a behavioral mania study, evaluating response to anti-polar disorder drugs, and performing a microarray study. Genes linked with BPD including P2rx7 have been identified in this strain.

Disclaimer: If MMRRC Strain Genetic Quality Control (GQC; based on MiniMUGA genotyping and analysis) has been completed for this strain, the information might differ from the genetic background information provided by the submitter. MiniMUGA genetic analysis is done on a strain's tissue samples taken when archived by or ordered from the assigned MMRRC Center.

Colony and Husbandry Information

Colony Surveillance Program and Current Health Reports

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email mmrrc@missouri.edu.
Coat Color
White
Eye
Red
Other
Smaller body weight relative to outbred Hsd:ICR (due in part to higher activity).
MMRRC Breeding System
Random intra-strain mating
Overall Breeding Performance
Good
Viability and Fertility: Female Male Comments
Homozygotes are viable: Yes Yes
Homozygotes are fertile: Yes Yes
Heterozygotes are fertile: Yes Yes
Age Reproductive Decline: 5 months Undetermined
Bred to Homozygosity
Yes
Average litter size
10-14
Recommended wean age
3 weeks

Order Information

Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

Cryopreserved material may be available upon request, please inquire to mmrrc@missouri.edu for more information.

Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

The submitter or their institution limits the distribution to non-profit institutions only.

Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # Description Distribution Fee / Unit (US $)
*Shipping & Handling not included*
Units Notes
036809-MU-EMBRYO Cryo-preserved embryos $1,038.00 / Non-Profit Aliquot Approximate quantity2 : 20-40 embryos / aliquot
036809-MU-RESUS Litter recovered from cryo-archive $2,028.00 / Non-Profit Litter Recovered litter4; additional fees for any special requests.
Cryopreserved material may be available upon request, please inquire to mmrrc@missouri.edu for more information.

1 The distribution fee covers the expense of rederiving mice from a live mouse; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

2 An aliquot contains a sufficient number of embryos (in one or more vials or straws and based on the transfer success rate of the MMRRC facility) to transfer into one to three recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

3 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.

4 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.