Strain Detail Sheet

Strain Name:
PdxMmmh:HDID2
Stock Number:
065278-MU
Citation ID:
RRID:MMRRC_065278-MU
Other Names:
HDID-2

Strain Information

Gene Details

Genetic Alterations
This is a selectively bred line, HDID-2. Mice were selectively bred over close to 40 generations to increase the blood ethanol concentration (BEC) achieved after drinking 20% alcohol during a 4-hour period. There is no single allele responsible. Rather, our work shows the influence of many genes on this phenotype.
Genotype Determination

Strain Description

Phenotype
HDID-2 mice were bred to voluntarily drink alcohol to the point of intoxication as measured by blood ethanol concentration (BEC) during a 4 hour period.
MeSH Terms
  • Animals
  • Binge Drinking/genetics
  • Ethanol/blood
  • Female
  • Inbreeding
  • Male
  • Mice
  • Selection, Genetic
  • Alcohol Drinking/genetics
  • Alcohol Drinking/metabolism
  • Basal Ganglia/metabolism
  • Brain Chemistry/genetics
  • Darkness
  • Gene Regulatory Networks
  • Quantitative Trait Loci
  • Behavior, Animal
  • Central Nervous System Depressants/blood
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Time Factors
  • Breeding
  • Circadian Rhythm/drug effects
  • Circadian Rhythm/genetics
  • Ethanol/administration & dosage
  • Ethanol/adverse effects
  • Hypothermia/chemically induced
  • Hypothermia/genetics
  • Mice, Transgenic
  • Reflex, Righting/drug effects
  • Reflex, Righting/genetics
  • Species Specificity
  • Alcohol Drinking/pathology
  • Drug Tolerance/genetics
  • Mice, Mutant Strains
  • Severity of Illness Index
  • Substance Withdrawal Syndrome/genetics
  • Substance Withdrawal Syndrome/pathology
  • Catalepsy/chemically induced
  • Cell Count
  • Dopamine/analysis
  • Haloperidol/pharmacology
  • Hybridization, Genetic
  • Phenotype
  • Substantia Nigra/cytology
  • Tyrosine 3-Monooxygenase/metabolism
  • Ventral Tegmental Area/cytology
Strain Development
This line (HDID-2) is one of two genetically independent replicate lines (HDID-1 and HDID-2) bred for high blood ethanol concentrations (BEC) after a procedure known as "drinking in the dark" (DID). This procedure offered the mice a 2-hr period in which to drink 20% v/v ethanol in tap water 3 hours into their dark cycle on Day #1. On Day #2, the period of access to ethanol was extended to 4 hours, with readings of consumption at 2 and at 4 hours. Immediately after reading the final consumption amount, the mice were blood-sampled (20 µl) from the periorbital sinus. This blood sample was assayed for BEC by gas chromatography, and mice that were the top 15-20 BECs of both sexes were selected for breeding the next generation.

Additional information in PMID:24219304.
Suggested Control Mice
HS/Npt; Heterogeneous Stock/Northport; developed by Dr. Robert J. Hitzemann (PMID:7965819)

MMRRC Genetic QC

MMRRC Genetic QC Summary
The MMRRC Centers have developed a genetic QC pipeline using MiniMUGA array genotyping to provide additional information on strain backgrounds for MMRRC congenic and inbred strains. For more information on when data may be available, or to request genotyping for a strain of interest, please contact mmrrc@missouri.edu. Older strains may not have this information.

Research Applications

  • Models for Human Disease

Strain Origin

Donor
John Crabbe, Ph.D., Oregon Health & Science University.
Pamela Metten, Ph.D., Oregon Health & Science University.
Primary Reference

Crabbe JC, Metten P, Belknap JK, Spence SE, Cameron AJ, Schlumbohm JP, HuangLC, Barkley-Levenson AM, Ford MM, Phillips TJ. Progress in a replicated selectionfor elevated blood ethanol concentrations in HDID mice. Genes Brain Behav. 2014Feb;13(2):236-46. doi: 10.1111/gbb.12105. Epub 2013 Dec 6. (Medline PMID: 24219304)

Iancu OD, Oberbeck D, Darakjian P, Metten P, McWeeney S, Crabbe JC, Hitzemann R. Selection for drinking in the dark alters brain gene coexpression networks.Alcohol Clin Exp Res. 2013 Aug;37(8):1295-303. doi: 10.1111/acer.12100. Epub 2013Mar 29. (Medline PMID: 23550792)

Crabbe JC, Harkness JH, Spence SE, Huang LC, Metten P. Intermittentavailability of ethanol does not always lead to elevated drinking in mice.Alcohol Alcohol. 2012 Sep-Oct;47(5):509-17. doi: 10.1093/alcalc/ags067. Epub 2012Jun 19. (Medline PMID: 22717273)

Crabbe JC, Kruse LC, Colville AM, Cameron AJ, Spence SE, Schlumbohm JP, Huang LC, Metten P. Ethanol sensitivity in high drinking in the dark selectively bredmice. Alcohol Clin Exp Res. 2012 Jul;36(7):1162-70. doi:10.1111/j.1530-0277.2012.01735.x. Epub 2012 Feb 8. (Medline PMID: 22316249)

Crabbe JC, Colville AM, Kruse LC, Cameron AJ, Spence SE, Schlumbohm JP, Huang LC, Metten P. Ethanol tolerance and withdrawal severity in high drinking in thedark selectively bred mice. Alcohol Clin Exp Res. 2012 Jul;36(7):1152-61. doi:10.1111/j.1530-0277.2011.01715.x. Epub 2012 Feb 6. (Medline PMID: 22309139)

Iancu OD, Colville AM, Wilmot B, Searles R, Darakjian P, Zheng C, McWeeney S, Kawane S, Crabbe JC, Metten P, Oberbeck D, Hitzemann R. Gender-Specific Effectsof Selection for Drinking in the Dark on the Network Roles of Coding andNoncoding RNAs. Alcohol Clin Exp Res. 2018 May 22. doi: 10.1111/acer.13777. [Epubahead of print] (Medline PMID: 29786871)

Hitzemann B, Dains K, Kanes S, Hitzemann R. Further studies on therelationship between dopamine cell density and haloperidol-induced catalepsy. JPharmacol Exp Ther. 1994 Nov;271(2):969-76. (Medline PMID: 7965819)

Colony and Husbandry Information

Health Status Report

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.

Appearance

Coat Color
Coat color is still segregating; however, agouti allele status is homozygous recessive
Eye
Eye color is still segregating
Other
This is the first selective breeding project that used a blood drug value for the selection index rather than behavior or physical characteristic. Furthermore, this unique genetic animal model drinks to higher blood ethanol concentrations than the standard inbred strain, C57BL/6J, that has been the highest preferring animal model. This second replicate (HDID-2) shows different ethanol drinking microstructure than the first replicate, HDID-1 (MMRRC:65277 - PMID:25981501). Importantly, drinking in the dark model has been adopted by many laboratories to mimic binge-like drinking in mice and has been adapted for other rodents (rats, voles, and hamsters). It is simple, minimally invasive, and does not require alcohol adulteration, thirst motivation, long periods of ramping up the ethanol concentration, administration by gavage, or other manipulations. The ethanol tube is placed on the cage of an individually housed mouse and the water is removed. When the drinking period is ended, water is restored. The mouse may choose whether or not to drink the ethanol.

Breeding

MMRRC Breeding System
Other or uncertain
Generation
S37
Overall Breeding Performance
Good

Reproductive Statistics

Viability and Fertility: Female Male Comments
Homozygotes are viable: Yes Yes
Homozygotes are fertile: N/A N/A
Heterozygotes are fertile: N/A N/A
Age Reproductive Decline: Undetermined Undetermined
Bred to Homozygosity
No
Average litter size
7-9
Recommended wean age
3 Weeks
Average Pups Weaned
5-9

Order Request Information

Availability Level

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.

Conditions of Distribution

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.

Fees

- Products for this strain are Not Yet Available for Ordering
- If you register interest in this strain, you will be notified when it becomes available for ordering.
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.