Overview

This spontaneous amino acid substitution in the third kinase domain is valuable for the study of semilunar valvulogenesis, mammary gland development, and other epidermal growth factor driven physiology.

Genetic overview

Genetic Background	Generation

Egfr^wa2

Allele Type	Gene Symbol	Gene Name
Spontaneous	Egfr	epidermal growth factor receptor

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Research Applications

Cancer Research
Dermatology Research
Developmental Biology Research
Endocrine Deficiency Research
Immunology, Inflammation and Autoimmunity Research
Neurobiology Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous mice for the waved 2 spontaneous mutation (Egfr^wa2) are recognizable at 2 to 3 days by curly whiskers. The first coat is waved but later coats are not; vibrissae usually remain curled and the guard hairs curved. Some homozygotes have eyelids open at birth. Fertile mutant females have smaller than normal mammary glands with reduced milk resulting in impaired lactation. Semilunar valvulogenesis is also abnormal, with a large majority of homozygotes on varied backgrounds displaying enlarged and thickened aortic valves.

Development

In 1933, or shortly thereafter, the waved 2 mutation arose spontaneously in the "abnormal Corpus callosum stock" held by Dr. Clyde Keeler at The Bussey Institute of Harvard Medical School. In 1935 waved 2 (Egfr^wa2) was received from Dr. Reed by Dr. G.D. Snell at the Jackson Laboratory. It was crossed to shaker 2 (Myo15^sh2) mice of Dr. C.C. Little at The Jackson Laboratory and waved 2 shaker 2 (Egfr^wa2 Myo15^sh2) mice were crossed to flexed-tail (f) mice received from the Bussey Institute in 1936. All three mutations were maintained in this stock. In 1947 this stock was returned after the fire to Dr. Snell from Dr. Walter Heston. The stock was maintained by non-sibling within-stock matings until 1960 when one outcross was made to C3H/HeJ. The stock was then sibling mated for 13 generations before 3 crosses were made to C57BL/6J, via backcross-intercross, and the stock was then non-sibling within-stock mated and in 1969 two lines were selected, Myo15^sh2 and Egfr^wa2 and flexed was dropped from these lines. In the Egfr^wa2 line a cross was made to B6.Cg-bc, a congenic strain then at N5, and the resulting stock, carrying a and Egfr^wa2 but not bc, was sibling mated to maintain Egfr^wa2 by forced heterozygosis. It was cryopreserved in 1986 with the common parent at F53. Because recovery of this bankstock proved very difficult this new subline was generated by recovering a few of the original cryopreserved embryos, expanding the colony by sibling breeding for 2 generations then generating cryopreserved embryos from homozygous males outcrossed to (C57BL/6J x C3H/HeJ)F1 females. Sperm was also cryopreserved from homozygous males and cryo-recovery will use (C57BL/6J x C3H/HeJ)F1 oocytes for IVF.

Selected References

Keeler CE. 1935. A second rexoid coat character in the house mouse. J Hered 26:189-191MGI: J:13052
Luetteke NC; Phillips HK; Qiu TH; Copeland NG; Earp HS; Jenkins NA; Lee DC. 1994. The mouse waved-2 phenotype results from a point mutation in the EGF receptor tyrosine kinase. Genes Dev 8(4):399-413PubMed: 8125255 MGI: J:16986

View All References

Genetics

Egfr^wa2

Allele Symbol: Egfr^wa2

Allele Name	waved 2
Allele Type	Spontaneous
Allele Synonym(s)	wa2; wa-2; waved2
Gene Symbol and Name	Egfr, epidermal growth factor receptor
Gene Synonym(s)
Strain of Origin	STOCK ac
Chromosome	11
General Note	Found by Keeler in an ``abnormal corpus callosum'' stock at the Bussey Institution.
Molecular Note	A T-to-G transversion mutation in the sequences encoding the tyrosine kinase domain results in a substitution of a highly conserved valine with glycine at position 767 (P.V767G) in the third kinase subdomain.

Disease/Phenotype

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

aortic valve disease

Research Areas By Phenotype

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

Genotype: Egfr^wa2 related

Cancer Research
- Growth Factors/Receptors/Cytokines
Dermatology Research
- Skin and Hair Texture Defects
Developmental Biology Research
- Neural Tube Defects
Endocrine Deficiency Research
- Skin Defects
Immunology, Inflammation and Autoimmunity Research
- Growth Factors/Receptors/Cytokines
Neurobiology Research
- Neural Tube Defects

Mammalian Phenotype Terms by Genotype

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

Genotype: Egfr^wa2/Egfr^wa2
STOCK ac

growth/size/body region phenotype

decreased body size

vision/eye phenotype

abnormal eye morphology
- Background Sensitivity - a squint and/or cataract phenotype occurs in this genotype with penetrance of 81 percent

cataract

integument phenotype

abnormal hair cortex keratinization
- cortex of hair shaft is thickened

abnormal hair medulla
- hairs have irregularities and narrowing of the medulla

curly vibrissae
- vibrissae are bent upon the second day and are distinctly curled by 4-5 days of age
- vibrissae remain curled event though coat waviness decreases or disappears

increased curvature of guard hairs
- guard hairs remain curved even though coat waviness decreases over time
- when coat is most waved, the guard hairs are frizzled

increased curvature of hairs
- occurs where the medulla is irregular and narrowed

short hair
- coat length remains shorter

short vibrissae

waved hair
- aggregation chimeras between Egfr^wa2/Egfr^wa2 and +/+ embryos result in a patchy distribution of waved and normal hair, suggesting that Egfr^wa2 acts locally in the hair follicle cells
- coat waviness increases from 4th to 6th weeks of age but decreases during 7-8 weeks of age
- waviness may disappear entirely or may be evident to a slight degree throughout life
- waviness of hair appears as soon as the coat develops, at 7-8 days of age

Genotype: Egfr^wa2/Egfr^wa2
B6EiC3Sn a/A-Egfr Wnt3a/J

cardiovascular system phenotype

enlarged aortic valve
- enlarged/thickened aortic valves

thick aortic valve

endocrine/exocrine gland phenotype

abnormal lactation
- reduction of milk within ducts of mammary glands and secretory vacuolation within lobules is less pronounced

abnormal mammary gland morphology
- small mammary glands and the ratio of gland to adipose tissue is reduced

integument phenotype

abnormal hair texture

abnormal lactation
- reduction of milk within ducts of mammary glands and secretory vacuolation within lobules is less pronounced

abnormal mammary gland morphology
- small mammary glands and the ratio of gland to adipose tissue is reduced

abnormal vibrissa morphology

Genotype: Egfr^wa2/Egfr^wa2
STOCK Egfr

cardiovascular system phenotype

abnormal aortic valve morphology
- aortic valve size ranges from unaffected to mildly or markedly thickened

abnormal semilunar valve morphology
- about 80% exhibit semilunar valve enlargement

aortic valve regurgitation
- valve abnormalities persist into adulthood causing moderate to severe regurgitation

increased left ventricle systolic pressure
- higher peak left ventricular systolic pressure and a trend towards increased +dP/dT

prolonged PR interval

prolonged RR interval

Genotype: Egfr^wa2/Egfr^wa2
involves: C57BL/6

cardiovascular system phenotype

abnormal aorta morphology
- aortic diameters at the level of the sinuses of Valsalva and at the level of the proximal ascending aorta are increased at all ages
- aortic enlargement at 1.5 months of age

abnormal aortic valve morphology
- alpha-smooth muscle actin levels are elevated in aortic valves at 6 and 12 months of age but not at 1.5 months, indicating transdifferentiation of valve interstitial cells from a quiescent state to a profibrotic state
- aortic valve collagen levels are normal at 1.5 months of age but are increased at 6 and 12 months of age
- Normal - however, levels of biglycan are normal
- intact versican is increased while cleaved versican is reduced in aortic valves at 6 months of age indicating increased levels of total proteoglycan
- levels of proteoglycan in the aortic valve are elevated at 1.5, 6, and 12 months of age
- lipid levels are increased in aortic valves at 6 and 12 months of age but not at 1.5 months
- pioglitazone treatment has no effect on collagen levels, on aortic valve lipid levels, on aortic valve alpha-smooth muscle actin levels, or on intact or cleaved versican levels

abnormal heart left ventricle morphology
- left ventricle mass, indexed to body mass, is elevated at 1.5, 6, and 12 months of age
- pioglitazone treatment has no effect on left ventricle mass

abnormal heart valve physiology
- an increase in apoptosis in the aortic valve is seen at 6 and 12 months of age, but not at 1.5 months
- elevation of transvalvular gradients in aortic valves
- Normal - treatment with pioglitazone prevents increases in apoptosis

abnormal myocardial fiber morphology
- myocardial transverse tubule organization is disrupted at 12 months of age but not at 1.5 and 3 months

aortic valve regurgitation
- all mice with aortic stenosis also have severe aortic regurgitation with diastolic prolapse of more than or equal to 1 valve cusps into the left ventricular outflow tract
- Normal - however, mitral regurgitation is absent
- pioglitazone treatment has no effect on prevalence of aortic regurgitation
- prevalence of moderate or severe aortic regurgitation is 70%, 81%, and 73% at 1.5, 6, and 12 months of age, respectively

aortic valve stenosis
- 3 of 55 mice show an aortic cup separation of <0.66 mm, indicating a low level of aortic stenosis
- Normal - aortic cusp separation is normal in most mice and aortic cusp movement is symmetrical at all ages

calcified aortic valve
- aortic valve calcification is increased at 6 and 12 months of age but not at 1.5 months
- marker analysis indicates osteogenic transformation in the aortic valve at 6 and 12 months of age but not at 1.5 months
- pioglitazone treatment reduces valve calcification

cardiac fibrosis
- fibrosis is evident in the myocardium at 12 months of age

decreased ventricle muscle contractility
- by 12 months of age, a trend toward greater left ventricular dilation and lower left ventricle ejection fraction in females than in males
- left ventricle ejection fraction is decreased by 12 months of age but not at 1.5 and 6 months of age
- right ventricle ejection fraction is decreased at 6 months of age

heart left ventricle hypertrophy
- left ventricle hypertrophy at 1.5 and 3 months of age, at a time when left ventricle systolic function is normal

increased cardiac stroke volume
- Normal - however, stroke volume is not increased in the 30% of mice that do not have aortic regurgitation at 1.5 months of age
- left ventricle stroke volume is increased at 1.5, 6, and 12 months of age
- pioglitazone treatment has no effect on left ventricle stroke volume

increased heart left ventricle size
- left ventricle chamber enlargement at 1.5, 6, and 12 months of age

increased pulse pressure
- increase in transvalvular gradients associated with increased aortic pulse pressure

growth/size/body region phenotype

heart left ventricle hypertrophy
- left ventricle hypertrophy at 1.5 and 3 months of age, at a time when left ventricle systolic function is normal

muscle phenotype

abnormal myocardial fiber morphology
- myocardial transverse tubule organization is disrupted at 12 months of age but not at 1.5 and 3 months

decreased ventricle muscle contractility
- by 12 months of age, a trend toward greater left ventricular dilation and lower left ventricle ejection fraction in females than in males
- left ventricle ejection fraction is decreased by 12 months of age but not at 1.5 and 6 months of age
- right ventricle ejection fraction is decreased at 6 months of age

heart left ventricle hypertrophy
- left ventricle hypertrophy at 1.5 and 3 months of age, at a time when left ventricle systolic function is normal

References

Keeler CE. 1935. A second rexoid coat character in the house mouse. J Hered 26:189-191MGI: J:13052
Luetteke NC; Phillips HK; Qiu TH; Copeland NG; Earp HS; Jenkins NA; Lee DC. 1994. The mouse waved-2 phenotype results from a point mutation in the EGF receptor tyrosine kinase. Genes Dev 8(4):399-413PubMed: 8125255 MGI: J:16986

Additional - Egfr^wa2 related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Sanger sequencing:Egfr-SEQ
- Genotyping resources and troubleshooting
Breeding Considerations

Some homozygotes may have open eyelids at birth.
- Additional Breeding and Husbandry Support
Citation
When using the STOCK Egfr^wa2/2J mouse strain in a publication, please cite the originating article(s) and include JAX stock #025184 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 for Egfr<wa2>

Related Products and Services

Frozen Mouse Embryo	STOCK Egfr<wa2>/2J	$2595.00
Frozen Mouse Embryo	STOCK Egfr<wa2>/2J	$2595.00
Frozen Mouse Embryo	STOCK Egfr<wa2>/2J	$3373.50
Frozen Mouse Embryo	STOCK Egfr<wa2>/2J	$3373.50

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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.

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Genetic overview

Research Applications

Base Price

Detailed Description

Development

Selected References

Egfrwa2

Allele Symbol: Egfrwa2

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Phenotype

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

Genotype: Egfrwa2 related

Mammalian Phenotype Terms by Genotype

Genotype: Egfrwa2/Egfrwa2STOCK ac

growth/size/body region phenotype

vision/eye phenotype

integument phenotype

Genotype: Egfrwa2/Egfrwa2B6EiC3Sn a/A-Egfr Wnt3a/J

cardiovascular system phenotype

endocrine/exocrine gland phenotype

integument phenotype

Genotype: Egfrwa2/Egfrwa2STOCK Egfr

cardiovascular system phenotype

Genotype: Egfrwa2/Egfrwa2involves: C57BL/6

cardiovascular system phenotype

growth/size/body region phenotype

muscle phenotype

References

Additional - Egfrwa2 related

Genotyping Protocols

Breeding Considerations

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

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Egfr^wa2

Allele Symbol: Egfr^wa2

Genotype: Egfr^wa2 related

Genotype: Egfr^wa2/Egfr^wa2
STOCK ac

Genotype: Egfr^wa2/Egfr^wa2
B6EiC3Sn a/A-Egfr Wnt3a/J

Genotype: Egfr^wa2/Egfr^wa2
STOCK Egfr

Genotype: Egfr^wa2/Egfr^wa2
involves: C57BL/6

Additional - Egfr^wa2 related