Overview

Also Known As:NGFI-A, Egr1 KO

These Egr1 knock-out mice may be useful for studying carcinogenesis, inflammation, atherosclerosis, scleroderma, ischemic injury, tissue repair, fibrosis, matrix remodeling and wound healing.

Donating Investigator

Jeffrey Milbrandt, Washington University School of Medicine, St. Louis

Genetic overview

Genetic Background	Generation

Egr1^tm1Jmi

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Egr1	early growth response 1

View Genetics

Research Applications

Immunology, Inflammation and Autoimmunity Research
Endocrine Deficiency Research
Internal/Organ Research
Cardiovascular Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

In this strain a coding exon upstream of the DNA-binding domain of the early growth response 1 (Egr1) gene is replaced with a neo cassette, abolishing gene function. Homozygous Egr1^-/- mice are viable and normal in size. Homozygous females are sterile, are absent of corpora lutea, and display a 30% reduction in the weight of the uterus. These mice exhibit an impaired inflammatory response, impaired wound healing, and attenuated dermal fibrosis after TGF-β or bleomycin stimulation. Macrophages from Egr1^-/- mice showed reduced TNF-α secretion when stimulated with TGF-β. These mice may be useful for studying carcinogenesis, inflammation, atherosclerosis, scleroderma, ischemic injury, tissue repair, fibrosis, matrix remodeling and wound healing.

Development

A targeting vector was designed to place a neomycin resistance (neo) cassette into a coding exon upstream of the DNA-binding domain of the early growth response 1 (Egr1) gene. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl⁺-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric males were bred to C57BL/6NTac females to generate a colony of Egr1^-/- mice. The Donating investigator confirms that these mice were backcrossed to C57BL/6NTac mice for 26 generations (see SNP note below). Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6NJ (Stock No. 005304) for at least one generation to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. 4 markers on 3 chromosomes, 6, 12, and 13, were found to be segregating, suggesting an incomplete backcross.

Control Suggestions

Wild-type from the colony

Approximate Controls

005304 C57BL/6NJ

Additional Information

Considerations for Choosing Controls

Selected References

Lee SL; Tourtellotte LC; Wesselschmidt RL; Milbrandt J. 1995. Growth and differentiation proceeds normally in cells deficient in the immediate early gene NGFI-A. J Biol Chem 270(17):9971-7PubMed: 7730380 MGI: J:24948

View All References

Genetics

Egr1^tm1Jmi

Allele Symbol: Egr1^tm1Jmi

Allele Name	targeted mutation 1, Jeffrey Milbrandt
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	egr-1-; Egr1^-; Egr-1⁰; Egr-1^ko; NGFI-A^-
Gene Symbol and Name	Egr1, early growth response 1
Gene Synonym(s)
Strain of Origin	129
Chromosome	18
General Note	ES cell line = AB1 (129S7/SvEvBrd-Hprt⁺) or D3 (129S2/SvPas).
Molecular Note	The gene was disrupted by insertion of a PGK-neo cassette into a coding exon upstream of the DNA-binding domain via homologous recombination. The targeted mutation introduces several stop codons resulting protein truncation upstream of the DNA-binding domain. Gene expression and protein product were not observed in homozygous mutant ES cells.
Mutations Made By	Jeffrey Milbrandt, Washington University School of Medicine, St. Louis

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

myelodysplastic syndrome

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Immunology, Inflammation and Autoimmunity Research
Endocrine Deficiency Research
- Skin Defects
Internal/Organ Research
- Wound Healing
  - delayed/impaired
Cardiovascular Research
- Atherosclerosis

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Egr1^tm1Jmi/Egr1^tm1Jmi
involves: 129

reproductive system phenotype

abnormal ovary morphology

abnormal reproductive system physiology

absent corpus luteum
- ovaries were similar in weight to wild-type

Leydig cell atrophy
- atrophic Leydig cells; however, spermatogenesis is normal

female infertility

abnormal ovulation
- ovulation could be induced by exogenous gonadotropins

absent estrous cycle
- females are anestrous

decreased uterus weight
- ~30% the weight of wild-type uterus

cardiovascular system phenotype

cardiac fibrosis
- fibrotic lesions in the heart regardless of treatment with adrenoreceptor agonists
- Normal - heart weight/body weight ratios are normal

abnormal vascular wound healing
- less neointimal expansion seen 28 days after endothelial denudation of the femoral artery than in controls

endocrine/exocrine gland phenotype

abnormal ovary morphology

Leydig cell atrophy
- atrophic Leydig cells; however, spermatogenesis is normal

absent corpus luteum
- ovaries were similar in weight to wild-type

homeostasis/metabolism phenotype

abnormal circulating progesterone level
- serum levels of progesterone are reduced, however serum levels of estradiol are normal

abnormal vascular wound healing
- less neointimal expansion seen 28 days after endothelial denudation of the femoral artery than in controls

decreased luteinizing hormone level
- LH undetected in females in the pituitary
- LH levels decreased in males in the pituitary
- LH levels did not increase after ovariectomy in the pituitary

Genotype: Egr1^tm1Jmi/Egr1^tm1Jmi
involves: 129 * C57BL/6

hematopoietic system phenotype

abnormal hematopoietic stem cell morphology
- no buildup of stem cells in the bone marrow
- level of circulating hematopoietic stem cells is dramatically increased
- two fold increase in hematopoietic stem cells in the S/G2-M phase of the cell cycle

abnormal leukocyte cell number
- mildly elevated

abnormal neutrophil morphology
- dysplastic neutrophils in bone marrow and spleen

abnormal microglial cell physiology
- elevated numbers of activated microglial cells an macrophage but fewer than in controls

increased bone marrow cell number

thrombocytopenia

abnormal erythropoiesis
- ineffective erythropoiesis in bone marrow and spleen

abnormal leukocyte morphology

increased spleen weight
- 15-20 fold increase in spleen weight
- expanded erythroid and myeloid cells in spleen

anemia

increased lymphocyte cell number

cellular phenotype

decreased mitotic index
- frequency of mitosis in the liver remains more or less constant from 48 to 72 hours after hepatectomy
- lower frequency of mitosis in the liver 48 hours after hepatectomy

abnormal mitosis
- mitosis impaired between metaphase and anaphase

homeostasis/metabolism phenotype

abnormal physiological response to xenobiotic
- serum alanine aminotransferase is not increased by ethanol feeding whereas levels increase 2 fold in controls
- Normal - no effect of ethanol diet on LPS sensitivity
- liver weight/body weight ratio does not increase with ethanol feeding as happens with controls
- TNF alpha levels remain constant with ethanol feeding whereas they increase 20 fold in controls

abnormal response to injury

delayed wound healing
- less collagen deposition
- fewer alpha smooth muscle cell positive myofibroblasts
- reduced rate of wound healing

decreased cerebral infarction size
- infarcts are much smaller in total area after temporary middle cerebral artery occlusion
- less edema than in controls
- neurological deficits are mild

abnormal circulating alanine transaminase level
- serum alanine aminotransferase is not increased by ethanol feeding whereas levels increase 2 fold in controls

increased incidence of tumors by chemical induction
- ENU treatment at 4 and 20 weeks weeks results in T-cell lymphomas in 53% of mice compared to 26% of controls treated at 3 weeks and 10% of controls treated at 20 weeks

abnormal homeostasis

abnormal tumor necrosis factor level
- TNF alpha levels remain constant with ethanol feeding whereas they increase 20 fold in controls

increased liver triglyceride level
- slightly elevated liver triglycerides with ethanol feeding

endocrine/exocrine gland phenotype

increased T cell derived lymphoma incidence
- ENU treatment at 4 and 20 weeks weeks results in T-cell lymphomas in 53% of mice compared to 26% of controls treated at 3 weeks and 10% of controls treated at 20 weeks
- mice with lymphomas do not develop myeloproliferative disease

immune system phenotype

abnormal microglial cell physiology
- elevated numbers of activated microglial cells an macrophage but fewer than in controls

decreased inflammatory response
- lower inflammatory response to four daily subcutaneous bleomycin injections
- lower inflammatory response to a single subcutaneous TGF beta injection

increased lymphocyte cell number

increased spleen weight
- expanded erythroid and myeloid cells in spleen
- 15-20 fold increase in spleen weight

abnormal leukocyte cell number
- mildly elevated

abnormal tumor necrosis factor level
- TNF alpha levels remain constant with ethanol feeding whereas they increase 20 fold in controls

abnormal leukocyte morphology

abnormal neutrophil morphology
- dysplastic neutrophils in bone marrow and spleen

integument phenotype

thick dermal layer
- reduced accumulation of alpha-smooth musclew actin myofibroblasts
- bleomycin induced dermal thickening more modest than in controls
- less collagen accumulation
- less sclerotic than controls

increased skin papilloma incidence
- skin tumors induced by treatment with DMBA and TPA appear to be papillomas

liver/biliary system phenotype

decreased liver regeneration
- Normal - hepatocellular proliferation after partial hepatectomy normal for first 36 hours
- proliferation is significantly reduced at 48 hours

increased liver triglyceride level
- slightly elevated liver triglycerides with ethanol feeding

abnormal liver size
- liver weight/body weight ratio does not increase with ethanol feeding as happens with controls

abnormal liver physiology

mammalian phenotype

immune system phenotype
- Normal - no effect of ethanol diet on LPS sensitivity

liver/biliary system phenotype
- Normal - ethanol feeding does not induce liver steatosis

respiratory system phenotype
- Normal - bleomycin induced lung pathologies are attenuated

neoplasm
- Normal - spontaneous tumors do not develop

neoplasm

increased incidence of tumors by chemical induction
- ENU treatment at 4 and 20 weeks weeks results in T-cell lymphomas in 53% of mice compared to 26% of controls treated at 3 weeks and 10% of controls treated at 20 weeks

increased skin papilloma incidence
- skin tumors induced by treatment with DMBA and TPA appear to be papillomas

increased T cell derived lymphoma incidence
- ENU treatment at 4 and 20 weeks weeks results in T-cell lymphomas in 53% of mice compared to 26% of controls treated at 3 weeks and 10% of controls treated at 20 weeks
- mice with lymphomas do not develop myeloproliferative disease

decreased tumor latency
- mice treated with the mutagen DMBA and tumor promoter TPA develop skin tumors around 8 weeks rather than 12.5 weeks as in controls

growth/size/body region phenotype

increased spleen weight
- expanded erythroid and myeloid cells in spleen
- 15-20 fold increase in spleen weight

postnatal growth retardation
- mild

nervous system phenotype

decreased cerebral infarction size
- neurological deficits are mild
- infarcts are much smaller in total area after temporary middle cerebral artery occlusion
- less edema than in controls

abnormal microglial cell physiology
- elevated numbers of activated microglial cells an macrophage but fewer than in controls

respiratory system phenotype

pulmonary interstitial fibrosis
- reduced

pulmonary fibrosis
- number and size of subpleural and interstitial fibrotic foci is reduced
- diminished collagen accumulation

vision/eye phenotype

increased eye anterior chamber depth
- deeper anterior chamber of the eye at 56 days of age

abnormal vision
- reduced refraction relative to controls

abnormal cornea morphology
- smaller radius of curvature at 40 days of age than in controls

abnormal eye anterior chamber depth
- deeper anterior chamber of the eye at 56 days of age

abnormal eye size
- longer eyes (axial eye length) than controls at 42 days of age

abnormal eye morphology

enlarged eye anterior chamber
- deeper anterior chamber of the eye at 56 days of age

The following phenotype relates to a compound genotype created using this strain

Genotype: Egr1^tm1Jmi/Egr1^tm1Jmi
B6.129-Egr1

hematopoietic system phenotype

increased osteoclast cell number
- elevated osteoclast formation regardless of estrogen levels

immune system phenotype

liver inflammation
- neutrophiles in parenchyma 50% lower than in controls
- reduced extravasation of neutrophiles in liver

abnormal circulating tumor necrosis factor level
- increase is 75% less 5.5 hours after treatment
- Normal - early increases after treatment with galactoseamine/LPS are similar to controls
- increase is 65% less 4 hours after treatment

increased osteoclast cell number
- elevated osteoclast formation regardless of estrogen levels

liver/biliary system phenotype

abnormal liver physiology
- survive 7 hours rather than 6 hours after galactoseamine/LPS treatment
- extensive liver hemorrhage and hepatocyte apoptosis by 7 hours

liver inflammation
- neutrophiles in parenchyma 50% lower than in controls
- reduced extravasation of neutrophiles in liver

mammalian phenotype

liver/biliary system phenotype
- Normal - galactoseamine/LPS induced liver injury is attenuated early
- Normal - very little hemorrhage
- Normal - no evidence of necrosis
- Normal - less evidence of apoptosis

cardiovascular system phenotype
- Normal - no atherosclerotic lesions at the root of the aorta

skeleton phenotype

decreased bone mineral density
- decreased 10% by 4 months of age

increased osteoclast cell number
- elevated osteoclast formation regardless of estrogen levels

abnormal trabecular bone morphology
- increased cancellous bone formation

homeostasis/metabolism phenotype

abnormal circulating tumor necrosis factor level
- increase is 65% less 4 hours after treatment
- increase is 75% less 5.5 hours after treatment
- Normal - early increases after treatment with galactoseamine/LPS are similar to controls

abnormal circulating alanine transaminase level
- 30% less increase in alanine aminotransferase levels in plasma after galactoseamine/LPS treatment than in controls

References

Lee SL; Tourtellotte LC; Wesselschmidt RL; Milbrandt J. 1995. Growth and differentiation proceeds normally in cells deficient in the immediate early gene NGFI-A. J Biol Chem 270(17):9971-7PubMed: 7730380 MGI: J:24948

Additional - Egr1^tm1Jmi related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated MCA:Egr1
- Separated PCR:Egr1
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, heterozygous mice may be bred to wildtype mice from the colony. Homozygous females are sterile.
- Additional Breeding and Husbandry Support
Mating System
- Wild-type x Heterozygote
- Heterozygote x Wild-type
Citation
When using the NGFI-A mouse strain in a publication, please cite the originating article(s) and include JAX stock #012924 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or wildtype for Egr1<tm1Jmi>

Related Products and Services

Frozen Mouse Embryo	B6N;129-Egr1<tm1Jmi>/J	$2595.00
Frozen Mouse Embryo	B6N;129-Egr1<tm1Jmi>/J	$2595.00
Frozen Mouse Embryo	B6N;129-Egr1<tm1Jmi>/J	$3373.50
Frozen Mouse Embryo	B6N;129-Egr1<tm1Jmi>/J	$3373.50

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:NGFI-A, Egr1 KO

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Egr1tm1Jmi

Allele Symbol: Egr1tm1Jmi

Disease Terms

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Egr1tm1Jmi/Egr1tm1Jmiinvolves: 129

reproductive system phenotype

cardiovascular system phenotype

endocrine/exocrine gland phenotype

homeostasis/metabolism phenotype

Genotype: Egr1tm1Jmi/Egr1tm1Jmiinvolves: 129 * C57BL/6

hematopoietic system phenotype

cellular phenotype

homeostasis/metabolism phenotype

endocrine/exocrine gland phenotype

immune system phenotype

integument phenotype

liver/biliary system phenotype

mammalian phenotype

neoplasm

growth/size/body region phenotype

nervous system phenotype

respiratory system phenotype

vision/eye phenotype

Genotype: Egr1tm1Jmi/Egr1tm1JmiB6.129-Egr1

hematopoietic system phenotype

immune system phenotype

liver/biliary system phenotype

mammalian phenotype

skeleton phenotype

homeostasis/metabolism phenotype

References

Additional - Egr1tm1Jmi related

Genotyping Protocols

Breeding Considerations

Mating System

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Egr1^tm1Jmi

Allele Symbol: Egr1^tm1Jmi

Genotype: Egr1^tm1Jmi/Egr1^tm1Jmi
involves: 129

Genotype: Egr1^tm1Jmi/Egr1^tm1Jmi
involves: 129 * C57BL/6

Genotype: Egr1^tm1Jmi/Egr1^tm1Jmi
B6.129-Egr1

Additional - Egr1^tm1Jmi related