Strain Name:
B6J.FVB-Tg(Chrna6*L280S)2Lst/Mmucd
Stock Number:
050701-UCD
Citation ID:
RRID:MMRRC_050701-UCD
Other Names:
C57BACCHRNA6 L9'S-Tg-2

Strain Information

Tg(Chrna6*L280S)2Lst
Name: transgene insertion 2, Henry Lester
Type: Allele
Species: Mus musculus (mouse)
Chromosome: unknown
Chrna6
Name: cholinergic receptor, nicotinic, alpha polypeptide 6
Synonyms: alpha6 nAChR, Acra6
Type: Gene
Species: Mouse
Chromosome: 8
NCBI: 11440
Homologene: 20888
Genetic Alterations
Selection of a 156-kb mouse BAC clone containing the genomic Chrna6 locus with substantial 5' and 3' flanking regions for generating a targeting construct to recapitulate expression of Chrna6. Residue Leu280 (M2 domain) was mutated to serine via homologous recombination using a 2-step selection/counterselection procedure in E. coli.

HGVS nomenclature:

  • Genbank RefSeq - mRNA: NM_021369.2
  • Genbank RefSeq, protein: NP_067344.2
  • Variant, nucleic acid level: c.838_840delinsTCA
  • Variant, amino acid level, predicted: p.Leu280Ser
  • Notes: There are additional, adjacent, silent genetic alterations
    Check the variant: LUMC Mualyzer
Genotype Determination
Phenotype
These mice are hyperactive in their home cage and fail to habituate to a novel environment. Selective activation of α6 nAChRs with low doses of nicotine by stimulating DA neurons exaggerates these phenotypes and produces a hyperdopaminergic state in vivo.
MeSH Terms
  • Animals
  • Chromosomes, Artificial, Bacterial/genetics
  • Dopamine/genetics
  • Dopamine/metabolism
  • Dopamine/physiology
  • Mesencephalon/chemistry
  • Mesencephalon/metabolism
  • Mice
  • Mice, Transgenic
  • Neurons/metabolism
  • Neurons/physiology
  • Receptors, Nicotinic/biosynthesis
  • Receptors, Nicotinic/genetics
  • Receptors, Nicotinic/metabolism
  • Receptors, Nicotinic/physiology
  • Recombination, Genetic
  • Synaptic Transmission/genetics
Strain Development
Per donor: We selected a 156-kb mouse BAC clone containing the genomic Chrna6 (α6 nAChR) locus with substantial 5' and 3'-flanking genomic regions for generating a targeting construct to faithfully recapitulate expression of Chrna6. α6Leu280 (M2 domain) was mutated to serine via homologous recombination using a two-step selection/counterselection procedure in E. coli. The final construct was injected into fertilized mouse eggs, and six transgenic offspring were identified by genomic DNA sequencing and diagnostic PCR. To eliminate possible artifacts of transgene position/insertion, we analyzed two independently derived lines, which have different transgene copy numbers and different genomic positions. Both mouse lines expressed mutant α6L9’S mRNA in addition to wild-type (WT) α6 mRNA. Founder #2 established the line donated to the MMRRC.
Suggested Control Mice
C57BL/6J
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@ucdavis.edu. Older strains may not have this information.
  • Models for Human Disease
  • Neurobiology
  • Research Tools
Donor
Henry Lester, Ph.D., California Institute of Technology.
Ryan Drenan, Ph.D., Northwestern University - Feinberg School of Medicine.
Primary Reference

Drenan RM, Grady SR, Whiteaker P, McClure-Begley T, McKinney S, Miwa JM, Bupp S, Heintz N, McIntosh JM, Bencherif M, Marks MJ, Lester HA. In vivo activation of midbrain dopamine neurons via sensitized, high-affinity alpha 6 nicotinic acetylcholine receptors. Neuron. 2008 Oct 9;60(1):123-36. doi: 10.1016/j.neuron.2008.09.009. (Medline PMID: 18940593)

Colony and Husbandry Information

Remove the male TG before birth so there isn’t an issue with the hyperactivity phenotype interfering with the development of the pups. When the TG mouse in the breeding pair (for this line) is the female, that can sometimes result in some lost litters. The female TGs aren’t the best mothers, perhaps related to the hyperactivity phenotype in this line. If you instead take males, you have more flexibility such as 1) avoiding this mothering issue, 2) being able to set up trios or to hop the male around to various cages, and 3) being able to remove the male TG before birth so there isn’t an issue with the hyperactivity phenotype interfering with development of the pups.

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@ucdavis.edu.
Coat Color
Black
Eye
Black
MMRRC Breeding System
Backcross
Generation
N10+ (C57BL/6J)
Overall Breeding Performance
Good
NOTE: "Hemizygote" as used here refers to males carrying a mutation on the X Chromosome or mice of either sex carrying an inserted transgene with no homologous allele on the other chromosome.
Viability and Fertility: Female Male Comments
Homozygotes are viable: Yes Yes
Homozygotes are fertile: Yes Yes
Hetero/Hemizygotes are fertile: Yes Yes
Age Reproductive Decline: 4 to 6 months 8 to 12 months
Bred to Homozygosity
No
Average litter size
4-6
Recommended wean age
3 Weeks
Average Pups Weaned
4-6

Order Request 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@ucdavis.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.

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
050701-UCD-SPERM Cryo-preserved spermatozoa $546.25 / $869.88
Non-Profit / For-Profit
Aliquot Approximate quantity3
050701-UCD-RESUS Litter recovered from cryo-archive $4,044.00 / $7,650.23
Non-Profit / For-Profit
Litter Recovered litter4; additional fees for any special requests.
Cryopreserved material may be available upon request, please inquire to mmrrc@ucdavis.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.