Strain Name:
STOCK Del(11Irf1-D11Mit23)1Rub Tg(A94G6)1Rub/Mmucd
Stock Number:
009995-UCD
Citation ID:
RRID:MMRRC_009995-UCD
Other Names:
450 kb-deletion 11/+ mice harboring human YAC A94G6 transgene

Strain Information

Del(11Irf1-D11Mit23)1Rub
Name: deletion, Chr 11, Edward M Rubin 1; deletion, Chr 11, Edward M Rubin 1
Synonyms: Del(11Irf1-Csf2)1Rub, Del1Rub, del11
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 11
Alteration at locus: Deletion
Csf2
Name: colony stimulating factor 2 (granulocyte-macrophage)
Synonyms: MGI-IGM, GMCSF, Csfgm, Gm-CSf
Type: Gene
Species: Mouse
Chromosome: 11
Alteration at locus: Deletion
NCBI: 12981
HGNC: HGNC:2434
Homologene: 600
Irf1
Name: interferon regulatory factor 1
Synonyms: Irf-1
Type: Gene
Species: Mouse
Chromosome: 11
Alteration at locus: Deletion
NCBI: 16362
HGNC: HGNC:6116
Homologene: 1658
Tg(A94G6)1Rub
Name: transgene insertion 1, Edward M Rubin
Type: Transgene
Species: Mus musculus (mouse)
Chromosome: unknown
Alteration at locus: Transgenic
Genetic Alterations
Heterozygous mice carrying a 450 kb deletion between Irf1 and Csfgm genes on mouse chromosome 11(del 11/+)were crossed with human YAC A94G6 transgenic mice to generate a mouse line in which the transgene complemented the deletion phenotype.

450 kb del 11/+ mice (MMRRC:009968): To delete the 450-kb genomic interval between Irf-1 and Csfgm, two loxP sites bracketing this region were introduced sequentially into embryonic stem (ES) cells. The first loxP site was introduced into the last exon of the Irf-1 gene by using a targeting vector containing a neomycin resistance (neor) gene, correctly targeted ES cells were identified by Southern blot analysis. The second loxP site was introduced 2 kb downstream of Csfgm into the first targeted ES cells via a targeting vector which contains tandemly linked bacterial hygromycin resistance and herpes simplex virus thymidine kinase (HSV-tk) (14) genes. Southern blot analysis of hygromycin resistant clones was used to identify those that had undergone the correct targeting events. Twelve of the doubly targeted ES clones were expanded and electroporated with the Cre recombinase-expressing plasmid pBS185. ES cells that had undergone Cre recombinase-mediated loxP recombination were identified by selecting for hygromycin sensitivity and 1-(2-deoxy-2-fluoro-b-D-arabinofuransyl)-5-iodouracil (FIAU) resistance. Cells surviving this selection were confirmed to contain the predicted 450-kb cis deletion (del11) by Southern blot analysis.

Human YAC A94G6 trancgenic mice: 450 kb human YAC A94G6 containing OCTN2 gene was injected into FVB fertilized eggs to generate YAC transgenic mice.
Phenotype
Homozygous: Human YAC A94G6 transgene complemented the deletion- induced abnormalities of homozygous null mice (del 11/del 11). The mice were indistinguishable in body weight and liver and heart size, life span, plasma and hepatic triglyceride levels, and hepatic VLDL-TG production from wild-type controls. Mice homozygous for the deletion (del 11/del 11) had a variety of abnormalities, including severe hypertriglyceridemi, hepatic and cardiac enlargement, growth retardation and premature mortality.

Heterozygous: Human YAC A94G6 transgene also complemented the deletion- induced abnormalities of heterozygous deletion mice (del 11/+). The mice were indistinguishable in body weight and liver and heart size, life span, plasma and hepatic triglyceride levels, and hepatic VLDL-TG production from wild-type controls.
Mammalian Phenotype Terms
Allelic Composition: Del(11Irf1-D11Mit23)1Rub/Del(11Irf1-D11Mit23)1Rub (Genetic Background: 129/Sv-Del(11Irf1-D11Mit23)1Rub )

Allelic Composition: Del(11Irf1-D11Mit23)1Rub/+ (Genetic Background: 129/Sv-Del(11Irf1-D11Mit23)1Rub )

MeSH Terms
  • Animals
  • Carnitine/metabolism
  • Carrier Proteins/genetics
  • Carrier Proteins/physiology
  • Chromosome Mapping
  • Chromosome Walking
  • Chromosomes, Human, Pair 5/genetics
  • Genetic Complementation Test
  • Humans
  • Hypertriglyceridemia/genetics
  • Hypertriglyceridemia/metabolism
  • Lipoproteins, VLDL/metabolism
  • Liver/metabolism
  • Membrane Proteins/genetics
  • Membrane Proteins/physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Organic Cation Transport Proteins
  • Phenotype
  • Sequence Deletion
  • Solute Carrier Family 22 Member 5
  • Species Specificity
  • Triglycerides/secretion
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.
  • Cardiovascular
  • Models for Human Disease
  • Research Tools
  • Defects in OCTN2 gene have been implicated as being responsible for primary carnitine deficiency in humans. The phenotypic screens and follow-up analyses of the del11/del11 mice facilitated the discovery of a novel and previously unappreciated aspect of the carnitine-deficient phenotype: the relationship between carnitine, hepatic triglyceride production, and OCTN2. The findings from studies of del11/del11 mice, coupled with reports of carnitine administration significantly reducing plasma triglyceride concentrations in hypertriglyceridemic hemodialysis patients as well as in patients with type IV hyperlipoproteinemia, provides genetic evidence in support of a critical role for carnitine transport in the regulation of plasma triglyceride metabolism. The analysis of the del11/del11 as well as the del11/+ mice suggest that reductions in carnitine, whose intracellular concentration appears to be affected by modest decreases in OCTN2 activity, leads to the shunting of fatty acids away from mitochondrial transport into triglyceride storage and secretory pools.
Donor
Edward M. Rubin, Director, JGI, MD, Ph.D., Lawrence Berkeley National Laboratory
Primary Reference
Zhu Y, Jong MC, Frazer KA, Gong E, Krauss RM, Cheng JF, Boffelli D, Rubin EM. Genomic interval engineering of mice identifies a novel modulator of triglyceride production. Proc Natl Acad Sci U S A. 2000 Feb 1;97(3):1137-42. (Medline PMID: 10655497)

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@ucdavis.edu.

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.

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MMRRC Item # Description Distribution Fee / Unit (US $)
*Shipping & Handling not included*
Units Notes
009995-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.