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Strain Detail Sheet

Strain Name:
FVB.129S4(B6)-Hif1atm1Jhu/CkaMmjax
Stock Number:
037489-JAX
Citation ID:
RRID:MMRRC_037489-JAX
Other Names:
Hif1alpha on FVB

Strain Information

Gene Details

Hif1atm1Jhu
Name: hypoxia inducible factor 1, alpha subunit; targeted mutation 1, Johns Hopkins University
Synonyms: Hif1a-
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 12
Alteration at locus: Knockout
Hif1a
Name: hypoxia inducible factor 1, alpha subunit
Synonyms: MOP1, HIF-1alpha, HIF1alpha, bHLHe78
Type: Gene
Species: Mouse
Chromosome: 12
Alteration at locus: Knockout
NCBI: 15251
HGNC: HGNC:4910
Homologene: 1171

Additional Resources
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Google
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Gene Ontology
BioGPS
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KOMP Phenotyping
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GeneCards
ClinGen
Genetic Alterations

HIF1 is a master regulator of homeostatic response to hypoxia. A targeting vector was designed to disrupt the mouse Hif1a (hypoxia inducible factor 1, alpha subunit) gene by homologous recombination resulting in the replacement of exon 2 by a PGK promoter–neomycin resistance gene. The knockout allele results in embryonic lethality by E11; embryos exhibit neural tube defects and cardiovascular malformations. On the diabetes-inducible FVB/N background, mice provide a tool for examining the role of hypoxia in diabetes.

Genotype Determination
ES Cell Line
J1

Strain Description

Phenotype
Hif1a (hypoxia inducible factor 1, alpha subunit) encodes the alpha subunit of a heterodimer that functions as a master regulator of homeostatic response to hypoxia. HIF1 is essential to embryonic vascularization, tumor angiogenesis and ischemic disease. Loss of HIF1A results in embryonic lethality by E11. Beginning at E8.5, some Hif1a null embryos appear abnormal, however, by E9 all null embryos are morphologically abnormal. Abnormal embryos are characterized by mesenchymal cell death resulting in failure of neural tube closure with cystic degeneration and prolapse of neural folds, hyperplasia of the presumptive myocardium, anomalous vascular structures in the cephalic mesenchyme, absent or hypoplastic branchial arch vessels, and abnormal dorsal aortae. Hif1atm1Jhu embryonic stem cells have reduced mRNA levels of glucose transporters, glycolytic enzymes, and vascular endothelial growth factor as well as impaired cellular proliferation.

On the FVB/N background streptozotocin (STZ) administration induces diabetes in Hif1a null mice providing a resource for examining the role of hypoxia in diabetes.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
Mammalian Phenotype Terms
Allelic Composition: Hif1atm1Jhu/Hif1atm1Jhu (Genetic Background: involves: 129S4/SvJae * C57BL/6 )
MeSH Terms
  • Animals
  • Blood Vessels/embryology
  • Cell Division/genetics
  • Cell Respiration/genetics
  • Cell Respiration/physiology
  • Cells, Cultured
  • DNA-Binding Proteins/genetics
  • DNA-Binding Proteins/metabolism
  • DNA-Binding Proteins/physiology
  • Embryo, Mammalian/metabolism
  • Embryo, Mammalian/pathology
  • Endothelial Growth Factors/genetics
  • Homeostasis/physiology
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Immunoblotting
  • Immunohistochemistry
  • Lymphokines/genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nuclear Proteins/genetics
  • Nuclear Proteins/metabolism
  • Nuclear Proteins/physiology
  • Oxygen/metabolism
  • Platelet Endothelial Cell Adhesion Molecule-1/analysis
  • RNA, Messenger/analysis
  • Stem Cells/metabolism
  • Time Factors
  • Transcription Factors/physiology
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
Strain GQC Summary
The MMRRC Centers have developed a Strain GQC pipeline using MiniMUGA array genotyping to provide additional information on strain backgrounds for MMRRC strains. For more information on whether data may be available, or to request genotyping for a strain of interest, please contact MMRRC_GeneticQC@med.unc.edu. Older strains may not have this information available.
Suggested Control Mice
Littermates of all relevant genotypes.

Research Applications

  • Cardiovascular
  • Developmental Biology
  • Diabetes

Strain Origin

Donor
Claudia Kappen, Ph.D., Pennington Biomedical Research Center.
Primary Reference

Iyer NV, Kotch LE, Agani F, Leung SW, Laughner E, Wenger RH, Gassmann M, Gearhart JD, Lawler AM, Yu AY, Semenza GL. Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1 alpha. Genes Dev. 1998 Jan 15;12(2):149-62. (Medline PMID: 9436976)

Strain Development
A targeting vector containing a neomycin resistance cassette was used to replace exon 2. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were bred to C57BL/6. Mice from the colony were transferred to Claudia Kappen at the Pennington Biomedical Research Institute and the allele was introgressed to FVB/N for at least 10 generations. Upon arrival, mice were bred to FVB/NJ for at least 1 generation to establish the colony.


Disclaimer: If MMRRC Strain Genetic Quality Control (GQC; based on MiniMUGA genotyping and analysis) has been completed for this strain, the information might differ from the genetic background information provided by the submitter. MiniMUGA genetic analysis is done on a strain’s tissue samples taken when archived by or ordered from the assigned MMRRC Center.

Colony and Husbandry Information

Health Status Report

Cryo-recovered strains distributed by the MMRRC at JAX are shipped to the customer from the Pathogen & Opportunistic-Free Animal Room G200 - see https://www.jax.org/jax-mice-and-services/customer-support/customer-service/animal-health/health-status-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 csmmrrc@jax.org.

Appearance

Coat Color
White

Breeding

MMRRC Breeding System
Backcross
Breeding Scheme(s)

Wild-type (FVB/N) female x Hemizygous male or reciprocal mating

Generation
N10+
Overall Breeding Performance
Good

Reproductive Statistics

Viability and Fertility: Female Male Comments
Homozygotes are viable: No No
Homozygotes are fertile: Undetermined Undetermined
Heterozygotes are fertile: Yes Yes
Age Reproductive Decline: Undetermined Undetermined
Average litter size
5-9
Recommended wean age
3-4 weeks

Order Request Information

Availability Level

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 csmmrrc@jax.org for more information.

Conditions of Distribution

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.

Fees

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
037489-JAX-SPERM Cryo-preserved spermatozoa $459.00 / Non-Profit Aliquot Approximate quantity3
037489-JAX-RESUS Litter recovered from cryo-archive $2,123.00 / Non-Profit Litter Recovered litter4; additional fees for any special requests.
Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org 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.