Strain Name:
FVB/NCrl-Rr41em1Axvi Rr3em2Axvi/Mmucd
Stock Number:
043912-UCD
Citation ID:
RRID:MMRRC_043912-UCD
Other Names:
hs119/hs121 double enhancer knockout, hs119/hs121 enhancer double knockout (KO), hs119/hs121 null, hs119/hs121 enhancer deletion, ultraconserved enhancer deletion, Arx enhancer deletion, FVB-Rr41em1AxviRr3em2Axvi

Strain Information

Rr41em1Axvi
Name: regulatory region 41; endonuclease-mediated mutation 1, Axel Visel
Synonyms: deltahs119
Type: Allele
Species: Mus musculus (mouse)
Chromosome: X
Alteration at locus: CRISPR
Rr3em2Axvi
Name: regulatory region 3; endonuclease-mediated mutation 2, Axel Visel
Synonyms: hs119/hs121
Type: Allele
Species: Mus musculus (mouse)
Chromosome: X
Alteration at locus: CRISPR
Rr3
Name: regulatory region 3
Synonyms: uc467, hs121
Type: DNA Segment
Species: Mus musculus (mouse)
Chromosome: X
Alteration at locus: CRISPR
Rr41
Name: regulatory region 41
Synonyms: hs119
Type: Regulatory Region
Species: Mus musculus (mouse)
Chromosome: X
Alteration at locus: CRISPR
Genetic Alterations
The hs119/hs121 double KO line was made by injecting single cell embryos from the hs119 knockout founder lines with the hs121 targeting components. The strain carries deletions for both the hs119 enhancer (chrX:93,408,080-93,410,222, with insertion of "GTC" to generate an AatII restriction site in place of the hs119 enhancer) and the hs121 enhancer (chrX:93,309,594-93,311,455) on the same haplotype. The enhancer control expression of Arx (MGI:1097716).
Genotype Determination
Phenotype

Homozygous: Not determined.

Hetero/Hemizygous: Both hs119/hs121 heterozygous-null females and hemizygous-null males are viable and fertile.hs119/hs121 hemizygous-null males display decreased Arx (MGI:1097716) expression in the ventral forebrain and ~15% reduction in body weight. Substantial alterations in neuron populations, including 1) almost complete loss of cholinergic neurons in the striatum, 2) decreased density of parvalbumin-expressing GABAergic interneurons in the cortex, 3) increase in vasointestinal peptide-expressing GABAergic interneurons in the cortex. Males from the hs119/121 deletion line are unusually aggressive and have to be housed singly to prevent injuries to cage mates.

MeSH Terms
  • Animals
  • Brain/abnormalities
  • Brain/embryology
  • Brain/metabolism
  • Conserved Sequence
  • Embryonic Development/genetics
  • Enhancer Elements, Genetic
  • Female
  • Gene Deletion
  • Homeodomain Proteins/genetics
  • Homeodomain Proteins/metabolism
  • Male
  • Mice
  • Transcription Factors/genetics
  • Transcription Factors/metabolism
Strain Development
The hs119/hs121 double knockout was generated via CRISPR/Cas9 genome editing by microinjecting targeting components for the hs121 (Rr3, MGI:4421015) into single-cell embryos from the hs119 knockout (Rr41, MGI:6110565) founder line. The hs119 deletion allele was generated by homology-driven repair using an oligo template, whereas the hs121 allele was generated by nonhomologous end-joining repair. Founders harboring the double deletions were mated to FVB/NCrl (Charles River Strain 207) to obtain hemizygous double KO males for phenotyping. Subsequent generations were outcrossed to FVB/NCrl for colony expansion and maintenance.
Suggested Control Mice
Wild-type littermates
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.
  • Developmental Biology
  • Models for Human Disease
  • Neurobiology
Donor
Axel Visel, Ph.D., Lawrence Berkeley National Laboratory.
Primary Reference

Dickel DE, Ypsilanti AR, Pla R, Zhu Y, Barozzi I, Mannion BJ, Khin YS,Fukuda-Yuzawa Y, Plajzer-Frick I, Pickle CS, Lee EA, Harrington AN, Pham QT,Garvin TH, Kato M, Osterwalder M, Akiyama JA, Afzal V, Rubenstein JLR, PennacchioLA, Visel A. Ultraconserved Enhancers Are Required for Normal Development. Cell. 2018 Jan 25;172(3):491-499.e15. doi: 10.1016/j.cell.2017.12.017. Epub 2018 Jan18. (Medline PMID: 29358049)

Colony and Husbandry Information

Heterozygous double KO males display a ~15% reduction in body weight. Males from line are unusually aggressive and have to be housed singly to prevent injuries to cagemates.

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.
The MMRRC at UC Davis performed microbita analysis on feces samples received from the donating investigator while the mice were still at their facility. There is a MMRRC Fecal Microbiota report available for this strain.If you are interested in having the MMRRC at UC Davis perform microbiota analysis once the line is established at your facility please contact mmrrc@ucdavis.edu.
Coat Color
White (albino)
MMRRC Breeding System
Other or uncertain
Breeding Scheme(s)
Outcrossed to wild-type FVB/NCrl mice
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: Undetermined X-linked
Homozygotes are fertile: Undetermined X-linked
Hetero/Hemizygotes are fertile: Yes Yes
Age Reproductive Decline: Undetermined Undetermined
Bred to Homozygosity
No
Average litter size
10-14
Recommended wean age
3 weeks
Average Pups Weaned
10-14

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.

The donor 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
043912-UCD-EMBRYO Cryo-preserved embryos $1,038.00 / Non-Profit Aliquot Approximate quantity2 : 20-40 embryos / aliquot
043912-UCD-SPERM Cryo-preserved spermatozoa $546.25 / Non-Profit Aliquot Approximate quantity3
043912-UCD-RESUS Litter recovered from cryo-archive $4,044.00 / Non-Profit Litter Recovered litter4; additional fees for any special requests.

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.