Strain Name:
B6.Cg-Apoetm1Unc Lipctm1Unc Tg(LIPC*S145G)1Ssf/Mmmh
Stock Number:
011858-MU
Citation ID:
RRID:MMRRC_011858-MU

Strain Information

Apoetm1Unc
Name: apolipoprotein E; targeted mutation 1, University of North Carolina
Synonyms: ApoE-KO, mE-, AopE(-), EKO, apoE-, apoE0, APOE KO, mEKO, epsilon-, Apoetm1Un
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 7
Alteration at locus: Knockout
Lipctm1Unc
Name: lipase, hepatic; targeted mutation 1, University of North Carolina
Synonyms: hl-, HL-deficient
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 9
Alteration at locus: Knockout
Apoe
Name: apolipoprotein E
Synonyms: Apoe
Type: Gene
Species: Mouse
Chromosome: 7
Alteration at locus: Knockout
NCBI: 11816
HGNC: HGNC:613
Homologene: 30951
Lipc
Name: lipase, hepatic
Synonyms: HL, Hpl
Type: Gene
Species: Mouse
Chromosome: 9
Alteration at locus: Knockout
NCBI: 15450
VEGA: 9
HGNC: HGNC:6619
Homologene: 199
LIPC
Name: lipase, hepatic
Type: Gene
Species: Homo sapiens (human)
Chromosome:
Alteration at locus: Knockout
Tg(LIPC*S145G)1Ssf
Name: transgene insertion 1, Silvia Santamarina-Fojo
Synonyms: HL-S145G
Type: Transgene
Species: Mus musculus (mouse)
Chromosome: unknown
Alteration at locus: Transgenic
Genetic Alterations
The Lipctm1Unc allele ("HL-ko") inserts a neomycin resistance cassette into exon 4 of the gene.

The Apoetm1Unc (ApoE knockout) allele is an insertion of a neomycin resistance cassette that deleted part of exon 3 and part of intron 3 of the Apoe gene.

Per submission information, the Tg(LIPC*S145G)1Ssf transgene carries the human hepatic lipase C gene with a variant that renders the protein catalytically inactive ("S145G"). The MMRRC cannot reconcile this information with any published reference human or mouse reference sequence. However, the positional information matches Uniprot record E7EUK6, which is unreviewed and based on protein level information. Two alternate isoforms are associated with this record, E7EUJ1 and P11150, of which the latter is reviewed and it links to NM_000236.2, an earlier version of the NCBI record for the human LIPC RefSeq NM_000236.3. An alignment shows that "serine145" is analogous to serine206 (c.616_618) in NM_000236.3. The serine>glycine substitution in the paper describing the transgene development (PMID:15304509) references PMID:9831632, which reports AGT>GGT. The corrected change is hence NM_000236.3:c.616A>G;p.(Ser206Gly) – see Mutalyzer, and the official name of this gene should be Tg(LIPC*S206G)1Ssf.
Genotype Determination
ES Cell Line

Knockout alleles: E14TG2a derived from 129P2/OlaHsd

Transgene: C57BL/6N background

Phenotype
Homozygous: Increased high-density lipoprotein cholesterol and decreased atherosclerosis compared to double-knockout control animals without the HL- S145G transgene.

Hemizygous: Similar to homozygous phenotype.
Mammalian Phenotype Terms
Allelic Composition: Apoetm1Unc/Apoetm1Unc (Genetic Background: B6.129P2-Apoetm1Unc )

Allelic Composition: Apoetm1Unc/Apoetm1Unc (Genetic Background: B6.129P2-Apoetm1Unc/J )

Allelic Composition: Apoetm1Unc/Apoetm1Unc (Genetic Background: B6.Cg-Apoetm1Unc Faslpr )

Allelic Composition: Apoetm1Unc/Apoetm1Unc (Genetic Background: either: B6.129P2-Apoetm1Unc/J or (involves: 129P2/OlaHsd * C57BL/6J * ICR) )

Allelic Composition: Apoetm1Unc/Apoetm1Unc (Genetic Background: involves: 129P2/OlaHsd )

Allelic Composition: Apoetm1Unc/Apoetm1Unc (Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 )

Allelic Composition: Apoetm1Unc/Apoetm1Unc (Genetic Background: involves: 129P2/OlaHsd * C57BL/6 )

Allelic Composition: Apoetm1Unc/Apoetm1Unc (Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA )

Allelic Composition: Apoetm1Unc/Apoetm1Unc (Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * FVB/N )

Allelic Composition: Apoetm1Unc/Apoetm1Unc (Genetic Background: Not Specified )

  • adipose tissue
  • hematopoietic system
  • homeostasis/metabolism
    • decreased circulating glucose level [MP:0005560]
    • increased circulating cholesterol level [MP:0005178]
    • increased circulating HDL cholesterol level [MP:0001556]
    • increased circulating LDL cholesterol level [MP:0000182]
    • increased circulating triglyceride level [MP:0001552]
    • increased circulating alkaline phosphatase level [MP:0002968]
    • improved glucose tolerance [MP:0005292]
  • immune system
    • increased susceptibility to bacterial infection [MP:0002412]
  • growth/size/body
Allelic Composition: Apoetm1Unc/Apoe+ (Genetic Background: involves: 129P2/OlaHsd * C57BL/6 )

Allelic Composition: Apoetm1Unc/Apoe+ (Genetic Background: Not Specified )

  • hematopoietic system
  • immune system
    • increased susceptibility to bacterial infection [MP:0002412]
Allelic Composition: Apoeshl/Apoetm1Unc (Genetic Background: involves: 129P2/OlaHsd * KOR )

Allelic Composition: Lipctm1Unc/Lipctm1Unc (Genetic Background: B6.129P2-Lipctm1Unc )

Allelic Composition: Lipctm1Unc/Lipctm1Unc (Genetic Background: involves: 129 )

Allelic Composition: Lipctm1Unc/Lipctm1Unc (Genetic Background: involves: 129P2/OlaHsd * C57BL/6J )

MeSH Terms
  • Animals
  • Apolipoprotein B-48
  • Apolipoproteins B/analysis
  • Apolipoproteins B/blood
  • Arteriosclerosis/etiology
  • Arteriosclerosis/prevention & control
  • Catalysis
  • Female
  • Humans
  • Ligands
  • Lipase/physiology
  • Lipolysis
  • Lipoproteins, LDL/metabolism
  • Lipoproteins, VLDL/metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
Strain Development

A recombinant DNA fragment containing the human apoE promoter, a human mutant hepatic lipase (LIPC, HL-S145G) cDNA, the poly(A) signal from the human apoE gene, and the hepatic and macrophage control regions of the apoE/apoC-I locus was injected into the male C57BL/6 pronuclei heterozygous for the Lipctm1Unc allele. The founder HL-S145G transgenic was bred to Lipctm1Unc homozygotes (obtained from N. Maeda, UNC Chapel Hill). The offspring were crossed to ApoE-knockout mice (Apoetm1Unc) in the C57BL/6 background (also obtained from N. Maeda) and bred to homozygosity for the KO alleles.

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@missouri.edu. Older strains may not have this information.
  • Cardiovascular
  • Metabolism
  • Models for Human Disease
Donor
Silvia Santamarina-Fojo, M.D., Ph.D., National Heart, Lung, and Blood Institute (NHLBI)
Primary Reference
Gonzalez-Navarro H, Nong Z, Amar MJ, Shamburek RD, Najib-Fruchart J, Paigen BJ, Brewer HB Jr, Santamarina-Fojo S. The ligand-binding function of hepatic lipase modulates the development of atherosclerosis in transgenic mice. J Biol Chem. 2004 Oct 29;279(44):45312-21. Epub 2004 Aug 10. (Medline PMID: 15304509)
Additional References

Piedrahita JA, Zhang SH, Hagaman JR, Oliver PM, Maeda N. Generation of mice carrying a mutant apolipoprotein E gene inactivated by gene targeting in embryonic stem cells. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4471-5. doi: 10.1073/pnas.89.10.4471. (Medline PMID: 1584779)

Homanics GE, de Silva HV, Osada J, Zhang SH, Wong H, Borensztajn J, Maeda N. Mild dyslipidemia in mice following targeted inactivation of the hepatic lipase gene. J Biol Chem. 1995 Feb 17;270(7):2974-80. doi: 10.1074/jbc.270.7.2974. (Medline PMID: 7852377)

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@missouri.edu.
MMRRC Breeding System
Random intra-strain mating
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: Unknown Unknown
Bred to Homozygosity
Yes
Recommended wean age
4 weeks
Average Pups Weaned

6 pups

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@missouri.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
011858-MU-SPERM Cryo-preserved spermatozoa $437.00 / $817.00
Non-Profit / For-Profit
Aliquot Approximate quantity3
011858-MU-RESUS Litter recovered from cryo-archive $2,016.00 / $4,103.00
Non-Profit / For-Profit
Litter Recovered litter4; additional fees for any special requests.
Cryopreserved material may be available upon request, please inquire to mmrrc@missouri.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.