Strain Detail Sheet
A targeting vector was designed to disrupt the mouse Hif1a gene by homologous recombination resulting in the replacement of exon 2 by a PGK promoter–neomycin resistance (neo) gene.
Homozygous: Embryonic lethal.
Hemizygous: FVB/N background allows for induction of diabetes.
Allelic Composition: Hif1atm1Jhu/Hif1atm1Jhu (Genetic Background: involves: 129S4/SvJae * C57BL/6 )- mortality/aging
- complete embryonic lethality during organogenesis [MP:0011098] [PMID:9436976]
- cardiovascular system
- abnormal blood vessel morphology [MP:0001614] [PMID:9436976]
- abnormal intersomitic vessel morphology [MP:0012253] [PMID:9436976]
- abnormal vascular development [MP:0000259] [PMID:9436976]
- abnormal dorsal aorta morphology [MP:0004787] [PMID:9436976]
- dilated dorsal aorta [MP:0004068] [PMID:9436976]
- absent pharyngeal arch arteries [MP:0012493] [PMID:9436976]
- pharyngeal arch artery hypoplasia [MP:0012492] [PMID:9436976]
- abnormal heart tube morphology [MP:0000270] [PMID:9436976]
- abnormal outflow tract development [MP:0006126] [PMID:9436976]
- abnormal myocardium layer morphology [MP:0005329] [PMID:9436976]
- disorganized myocardium [MP:0002190] [PMID:9436976]
- abnormal heart ventricle morphology [MP:0005294] [PMID:9436976]
- abnormal pericardial cavity morphology [MP:0012501] [PMID:9436976]
- abnormal pericardium morphology [MP:0000288] [PMID:9436976]
- pericardial effusion [MP:0005312] [PMID:9436976]
- embryogenesis
- absent pharyngeal arch arteries [MP:0012493] [PMID:9436976]
- pharyngeal arch artery hypoplasia [MP:0012492] [PMID:9436976]
- abnormal head mesenchyme morphology [MP:0011260] [PMID:9436976]
- open neural tube [MP:0000929] [PMID:9436976]
- incomplete somite formation [MP:0001689] [PMID:9436976]
- embryonic growth arrest [MP:0001730] [PMID:9436976]
- nervous system
- open neural tube [MP:0000929] [PMID:9436976]
- increased hindbrain size [MP:0012265] [PMID:9436976]
- craniofacial
- absent pharyngeal arch arteries [MP:0012493] [PMID:9436976]
- pharyngeal arch artery hypoplasia [MP:0012492] [PMID:9436976]
- cellular
- increased apoptosis [MP:0006042] [PMID:9436976]
- homeostasis/metabolism
- pericardial effusion [MP:0005312] [PMID:9436976]
- growth/size/body
- abnormal head mesenchyme morphology [MP:0011260] [PMID:9436976]
- 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
The Hif1a mutant allele was generated by injecting correctly targeted J1 ES cells derived from 129S4/SvJae into C57BL/6 blastocysts. Blastocysts were then surgically implanted into the uterus of pseudopregnant CD1 foster mothers to produce chimeras. Germ-line transmission was obtained when chimeric males were mated to C57BL/6 females. This allele was then backcrossed onto the FVB/N background for more than 10 generations.
- Cardiovascular
- Developmental Biology
- Diabetes
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)
Wild-type (FVB/N) female x Hemizygous male or reciprocal mating
| 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 |
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.
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.
| MMRRC Item # | Description | Distribution Fee / Unit (US $) | Units | Notes |
|---|---|---|---|---|
| 037489-JAX-SPERM | Cryo-preserved spermatozoa | $437.00 / Non-Profit | Aliquot | Approximate quantity3 |
| 037489-JAX-RESUS | Litter recovered from cryo-archive | $2,022.00 / 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.