Strain Name:
B6J;129S6-Rr69tm1Axvi/Mmucd
Stock Number:
065565-UCD
Citation ID:
RRID:MMRRC_065565-UCD
Other Names:
hs2295 enhancer deletion knockout, intestine-critical region (ICR) deletion, ICR knockout, ICR-null mice, chr17<ΔICR>, B6;129S6-Rr69

Strain Information

Rr69tm1Axvi
Name: regulatory region 69; targeted mutation 1, Axel Visel
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 1
Alteration at locus: Knockout
Percc1
Name: proline and glutamate rich with coiled coil 1
Synonyms: Gm38655
Type: Gene
Species: Mus musculus (mouse)
Chromosome: 17
Alteration at locus: Knockout
NCBI: 102643076
VEGA: 17
Rr69
Name: regulatory region 69
Synonyms: hs2295, ICR
Type: Regulatory Region
Species: Mus musculus (mouse)
Chromosome: 17
Alteration at locus: Knockout
Genetic Alterations
Using homologous recombination in ESCs, 1512 bp of the hs2295 enhancer (ICR) were deleted.

Note: This work on ICR, a previously unstudied regulatory region, also allowed the identification of a new gene (Percc1) that is critical for intestinal function.
Genotype Determination
ES Cell Line
W4 derived from 129S6/SvEvTac
Phenotype
Starting within the first few days of life, homozygous pups for the hs2295 (or ICR) enhancer deletion display overall reduce size, low body weight, and substantially decreased survival compared to control littermates. Analyses reveal abnormal digestive-tract function and changes in the composition of the intestinal microbiome. The deletion of the hs2295 enhancer (or intestine-critical region, ICR) in homozygotes mice recapitulates the human syndrome known as intractable diarrhea of infancy syndrome (IDIS).
MeSH Terms
  • Animals
  • Chromosomes, Human, Pair 16/genetics
  • Diarrhea/congenital
  • Diarrhea/genetics
  • Disease Models, Animal
  • Enhancer Elements, Genetic/genetics
  • Female
  • Gene Expression Regulation, Developmental
  • Genes
  • Genes, Reporter
  • Genetic Loci/genetics
  • Humans
  • Intestines/physiology
  • Male
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Pedigree
  • Phenotype
  • Sequence Deletion/genetics
  • Transcriptional Activation
  • Transcriptome/genetics
  • Transgenes/genetics
Strain Development
The hs2295 (aka intestine-critical region, ICR) enhancer was targeted for deletion by homologous recombination by electroporation into W4/129S6 mouse embryonic stem cells. After selection, correctly targeted clones were microinjected into C57BL/6J embryos at the blastocyst stage. Chimeric mice were mated to C57BL/6J and 129S6/SvEvTac mice to generate heterozygous ICR-null mice, followed by breeding of heterozygous littermates to generate homozygous null mice.
Suggested Control Mice
Littermate mice genotyped as having no deletion of the hs2295 enhancer.
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
  • Internal/Organ
  • Models for Human Disease
Donor
Axel Visel, Ph.D., Lawrence Berkeley National Laboratory.
Primary Reference

Oz-Levi D, Olender T, Bar-Joseph I, Zhu Y, Marek-Yagel D, Barozzi I,Osterwalder M, Alkelai A, Ruzzo EK, Han Y, Vos ESM, Reznik-Wolf H, Hartman C,Shamir R, Weiss B, Shapiro R, Pode-Shakked B, Tatarskyy P, Milgrom R, Schvimer M,Barshack I, Imai DM, Coleman-Derr D, Dickel DE, Nord AS, Afzal V, van Bueren KL, Barnes RM, Black BL, Mayhew CN, Kuhar MF, Pitstick A, Tekman M, Stanescu HC,Wells JM, Kleta R, de Laat W, Goldstein DB, Pras E, Visel A, Lancet D, AniksterY, Pennacchio LA. Noncoding deletions reveal a gene that is critical forintestinal function. Nature. 2019 Jun 19. doi: 10.1038/s41586-019-1312-2. [Epubahead of print] (Medline PMID: 31217582)

Colony and Husbandry Information

Although the severity of the phenotype is heterogeneous, homozygote mice are very easy to spot by their small size and failure to thrive. Cages with newborn pups should be monitored daily. Once spotted, homozygote mice may need to be euthanized depending on their condition.

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
Because of their mixed B6J;129S6 background, most mice have a brown coat but some are black.
Eye
Black
MMRRC Breeding System
Sib-mating
Generation
F10
Overall Breeding Performance
Undetermined
Viability and Fertility: Female Male Comments
Homozygotes are viable: Reduced Reduced
Homozygotes are fertile: Undetermined Undetermined
Heterozygotes are fertile: Yes Yes
Age Reproductive Decline: Undetermined Undetermined
Bred to Homozygosity
Yes
Average litter size
7 to 9
Recommended wean age
3 Weeks
Average Pups Weaned
4 to 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.

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

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
065565-UCD-SPERM Cryo-preserved spermatozoa $546.25 / Non-Profit Aliquot Approximate quantity3
065565-UCD-RESUS Litter recovered from cryo-archive $4,044.00 / Non-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.