Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Background Strain CD1 Donor Strain 129S2 via D3 ES cell line Generation ?N1F2   Donating Investigator David Threadgill,   Lineberger Cancer Center 11-129

Appearance
albino
Related Genotype: unknown

Description
Mice homozygous for the Egfr^tm1Mag targeted mutation 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. Fertile mutant females have impaired lactation.

Development
This strain was developed in the laboratory of Dr. David Threadgill at Case Western Reserve University. The 129-derived D3 ES cell line was used.

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Egfr

000553	B6EiC3Sn a/A-Egfrwa2 Wnt3avt/J
006926	C57BL/6J-EgfrVel/J
000317	STOCK a/a Egfrwa2/J

View Strains carrying other alleles of Egfr     (3 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Egfr^tm1Mag/Egfr^tm1Mag

        involves: 129S2/SvPas * CD-1

• lethality-prenatal/perinatal
• *normal* lethality-prenatal/perinatal (MGI Ref ID J:26833)
  • homozygotes exhibit peri-implantation lethality on a CF1 background, mid-gestation lethality on an inbred 129/Sv background, and perinatal lethality on a CD-1 background
• perinatal lethality (MGI Ref ID J:26833)
  • on a CD-1-enriched genetic background, homozygotes die perinatally; however, survival can be extended up to P18 upon removal of wild-type littermates
• growth/size phenotype
• cachexia (MGI Ref ID J:26833)
  • homozygous mutant pups exhibit progressive wasting; postnatal survivors are only 30-35% the weight of wild-type littermates
• postnatal growth retardation (MGI Ref ID J:26833)
  • homozygous mutant pups exhibit a 15% reduction in postnatal growth, despite normal birth weights
• vision/eye phenotype
• absent eyelids (MGI Ref ID J:26833)
  • at E14.5-E18.5, homozygotes fail to form eyelids
• eyelids open at birth (MGI Ref ID J:26833)
  • homozygotes have open eyes at birth
• touch/vibrissae phenotype
• curly vibrissae (MGI Ref ID J:26833)
  • mutant whiskers are fragile and appear to curl anteriorly
• wavy vibrissae (MGI Ref ID J:26833)
  • homozygous mutant pups display rudimentary waved whiskers
• skin/coat/nails phenotype
• abnormal coat appearance (MGI Ref ID J:26833)
  • homozygotes have a fuzzy coat
• abnormal hair follicle structure/orientation (MGI Ref ID J:26833)
  • by P5, mutant hair follicles appear disoriented
• abnormal hair follicle development (MGI Ref ID J:26833)
  • by P2, homozygotes show a decline in interfollicular epidermal proliferation, reaching only 38% of the wild-type labeling index at P8
• abnormal hair follicle root sheath (MGI Ref ID J:26833)
  • by P5, the mutant inner root sheath display premature hair keratinization and maturation
• distorted hair follicle pattern (MGI Ref ID J:26833)
  • by P5, mutant hair follicles are abnormally placed
• abnormal hair shaft morphology (MGI Ref ID J:26833)
  • by P5, the mutant hair shaft shows premature separation from the inner root sheath
• delayed hair appearance (MGI Ref ID J:26833)
  • homozygotes exhibit a delay in the appearance of emerging hair
• digestive/alimentary phenotype
• abnormal colon morphology (MGI Ref ID J:26833)
  • although normal through P12, the mutant colonic epithelium displays an aberrant glandular architecture by P18
  • at P18, tall disorganized branching crypt columns are occasionally found close to short rudimentary crypt columns
• abnormal esophageal epithelium morphology (MGI Ref ID J:26833)
  • at P12 and P18, homozygotes display decreased BrdU labeling in the basal layer of the esophagus
• abnormal tongue morphology (MGI Ref ID J:26833)
  • mutant tongues contain reduced interspersed adipose tissue
• abnormal filiform papillae (MGI Ref ID J:26833)
  • homozygotes display abnormal filiform papillae with reduced connective tissue
• abnormal fungiform papillae (MGI Ref ID J:26833)
  • homozygotes show a reduction in the number of fungiform papillae
  • those present at P12 appear disorganized and lack identifiable taste buds
• liver/biliary system phenotype
• abnormal liver morphology (MGI Ref ID J:26833)
  • although normal at E17.5, mutant livers show aberrant sinusoidal anatomy and abnormal vacuolizatized nuclei by P8
• abnormal hepatocyte morphology (MGI Ref ID J:26833)
  • by P8, mutant livers display thickened hepatocyte cords
• renal/urinary system phenotype
• dilated kidney collecting duct (MGI Ref ID J:26833)
  • homozygotes exhibit cystic dilation of collecting tubules, with a flattened instead of a cuboidal epithelial lining
• homeostasis/metabolism phenotype
• increased blood urea nitrogen level (MGI Ref ID J:26833)
  • at P12, homozygotes display 75 mg/dl BUN vs 26 mg/dl in wild-type littermates; BUN reaches 288 mg/dl at P18
• increased circulating creatinine level (MGI Ref ID J:26833)
  • at P18, homozygotes display increased serum creatinine levels relative to wild-type littermates (2.4 mg/dl vs 0.1 mg/dl, respectively)
• nervous system phenotype
• abnormal cerebral cortex morphology (MGI Ref ID J:26833)
  • at E18.5, the mutant cerebral cortex appears relatively normal; however, neuroblast migration and cortical plate formation is impaired
  • at E18.5, the mutant ventricular zone is thickened while the intermediate zone is markedly thinned in some mutants
• thin cerebral cortex (MGI Ref ID J:26833)
  • by P18, homozygotes display atrophy of the anterior cerebral cortex, which is reduced to a thin sheet of cells
• abnormal external granule cell layer morphology (MGI Ref ID J:26833)
  • after birth, homozygotes exhibit delayed migration of the EGC layer
• abnormal olfactory bulb morphology (MGI Ref ID J:26833)
  • at E18.5, mutant olfactory bulbs appear normal in size and cell composition; however, by P14, mitral and tufted cells are nearly absent
  • at P18, homozygotes show a shorter or absent molecular layer; in contrast, glomerular structures remain unaffected
• decreased Purkinje cell number (MGI Ref ID J:26833)
  • at E18.5 and postnatally, the mutant cerebellar plate contains fewer Purkinje cells
• decreased brain size (MGI Ref ID J:26833)
  • at E18.5, homozygotes display a reduction in overall brain size; cortical regions are most affected
• small cerebellum (MGI Ref ID J:26833)
• respiratory system phenotype
• abnormal lung development (MGI Ref ID J:26833)
  • at E18.5, 2 of 8 homozygotes show slightly immature lung histology and weaker surfactant staining possibly due to overall growth retardation

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Egfr^tm1Mag/Egfr^tm1Mag

        involves: 129S2/SvPas * CF1

• lethality-prenatal/perinatal
• *normal* lethality-prenatal/perinatal (MGI Ref ID J:26833)
  • homozygotes exhibit peri-implantation lethality on a CF1 background, mid-gestation lethality on an inbred 129/Sv background, and perinatal lethality on a CD-1 background
• embryonic lethality before somite formation (MGI Ref ID J:26833)
  • on a CF1-enriched genetic background, homozygotes die before E7.5; only 2% of homozygotes are obtained at E6.5
• embryogenesis phenotype
• abnormal inner cell mass (MGI Ref ID J:26833)
  • at E4.5-E4.8, 6 of 32 homozygotes exhibit small, loosely arranged inner cell masses with no distinct endoderm
  • at E5.1-E5.5, 13 of 61 mutant embryos are collapsed; by E6.5, 8 of 31 decidua lack an embryo and are filled with maternal blood

Egfr^tm1Mag/Egfr^tm1Mag

        involves: 129/Sv * 129S2/SvPas

• lethality-prenatal/perinatal
• *normal* lethality-prenatal/perinatal (MGI Ref ID J:26833)
  • homozygotes exhibit peri-implantation lethality on a CF1 background, mid-gestation lethality on an inbred 129/Sv background, and perinatal lethality on a CD-1 background
• embryonic lethality during organogenesis (MGI Ref ID J:26833)
  • on a 129/Sv-enriched genetic background, homozygotes die at midgestation with resorbing embryos evident at E12.5-E13.5
• embryogenesis phenotype
• abnormal placenta labyrinth morphology (MGI Ref ID J:26833)
  • at E12.5-E13.5, the labyrinthine trophoblast appears disorganized and hypoplastic
  • in contrast, the organization and cell number of the trophoblast giant-cell layer is unremarkable
• abnormal spongiotrophoblast layer morphology (MGI Ref ID J:26833)
  • at E12.5-E13.5, the mutant spongiotrophoblast is significantly reduced
• decreased trophoblast giant cell number (MGI Ref ID J:26833)
  • at E12.5-E13.5, the labyrinthine trophoblast cell number is reduced
• small placenta (MGI Ref ID J:26833)
  • at E12.5-E13.5, mutant placentas are smaller than wild-type

View Research Applications

Research Applications

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

Egfr^tm1Mag related

Cancer Research
Growth Factors/Receptors/Cytokines

Dermatology Research
Skin and Hair Texture Defects

Developmental Biology Research
Internal/Organ Defects (kidney, brain, liver, GI)

Endocrine Deficiency Research
Skin Defects

Immunology and Inflammation Research
Growth Factors/Receptors/Cytokines

Internal/Organ Research
Kidney Defects
Liver Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Egfrtm1Mag
Allele Name		targeted mutation 1, Terry Magnuson
Allele Type		Targeted (knock-out)
Common Name(s)		EGFR-; Egfrm1Cwr;
Mutation Made By		Terry Magnuson,   Case Western Reserve University
Strain of Origin		129S2/SvPas
ES Cell Line Name		D3
ES Cell Line Strain		129S2/SvPas
Gene Symbol and Name		Egfr, epidermal growth factor receptor
Chromosome		11
Gene Common Name(s)		9030024J15Rik; AI552599; ERBB; ERBB1; ErbB-1; Erbb; Errp; HER1; PIG61; RIKEN cDNA 9030024J15 gene; Wa5; avian erythroblastic leukemia viral (v-erb-b) oncogene homolog; avian erythroblastosis oncogene B; expressed sequence AI552599; mENA; wa-2; wa2; waved 2; waved 5;
Molecular Note		A neomycin resistance cassette replaced 155 bp containing part of exon 2. Aberrant splicing of the targeted exon was detected joining exon 1 to either exon 3 or exon 5. The former splicing event creates a nonsense protein. Although the latter splicing event produes a truncated mRNA, no protein or phosphorylation activity was detectable. [MGI Ref ID J:26833]

Genotyping

Genotyping Information

Genotyping Protocols

Egfr^tm1Mag, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Threadgill DW; Dlugosz AA; Hansen LA; Tennenbaum T; Lichti U; Yee D; LaMantia C; Mourton T; Herrup K; Harris RC; Barnard JA; Yuspa SH; Coffey RJ; Magnuson T. 1995. Targeted disruption of mouse EGF receptor: effect of genetic background on mutant phenotype. Science 269(5221):230-4. [PubMed: 7618084]  [MGI Ref ID J:26833]

Additional References

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):399-413. [PubMed: 8125255]  [MGI Ref ID J:16986]

Egfr^tm1Mag related

Chen B; Bronson RT; Klaman LD; Hampton TG; Wang JF; Green PJ; Magnuson T; Douglas PS; Morgan JP; Neel BG. 2000. Mice mutant for Egfr and Shp2 have defective cardiac semilunar valvulogenesis. Nat Genet 24(3):296-9. [PubMed: 10700187]  [MGI Ref ID J:60750]

Dackor J; Strunk KE; Wehmeyer MM; Threadgill DW. 2007. Altered trophoblast proliferation is insufficient to account for placental dysfunction in Egfr null embryos. Placenta 28(11-12):1211-8. [PubMed: 17822758]  [MGI Ref ID J:141339]

Dise RS; Frey MR; Whitehead RH; Polk DB. 2008. Epidermal growth factor stimulates Rac activation through Src and phosphatidylinositol 3-kinase to promote colonic epithelial cell migration. Am J Physiol Gastrointest Liver Physiol 294(1):G276-85. [PubMed: 17991704]  [MGI Ref ID J:130505]

Dlugosz AA; Hansen L; Cheng C; Alexander N; Denning MF; Threadgill DW ; Magnuson T ; Coffey RJ Jr ; Yuspa SH. 1997. Targeted disruption of the epidermal growth factor receptor impairs growth of squamous papillomas expressing the v-ras(Ha) oncogene but does not block in vitro keratinocyte responses to oncogenic ras. Cancer Res 57(15):3180-8. [PubMed: 9242447]  [MGI Ref ID J:42403]

El-Abaseri TB; Fuhrman J; Trempus C; Shendrik I; Tennant RW; Hansen LA. 2005. Chemoprevention of UV light-induced skin tumorigenesis by inhibition of the epidermal growth factor receptor. Cancer Res 65(9):3958-65. [PubMed: 15867397]  [MGI Ref ID J:98332]

El-Abaseri TB; Putta S; Hansen LA. 2006. Ultraviolet irradiation induces keratinocyte proliferation and epidermal hyperplasia through the activation of the epidermal growth factor receptor. Carcinogenesis 27(2):225-31. [PubMed: 16123117]  [MGI Ref ID J:105099]

Gallego MI; Binart N; Robinson GW; Okagaki R; Coschigano KT; Perry J; Kopchick JJ; Oka T; Kelly PA; Hennighausen L. 2001. Prolactin, growth hormone, and epidermal growth factor activate Stat5 in different compartments of mammary tissue and exert different and overlapping developmental effects. Dev Biol 229(1):163-75. [PubMed: 11133161]  [MGI Ref ID J:66900]

Hansen LA; Alexander N; Hogan ME; Sundberg JP; Dlugosz A; Threadgill DW ; Magnuson T ; Yuspa SH. 1997. Genetically null mice reveal a central role for epidermal growth factor receptor in the differentiation of the hair follicle and normal hair development. Am J Pathol 150(6):1959-75. [PubMed: 9176390]  [MGI Ref ID J:40807]

Hansen LA; Woodson RL 2nd; Holbus S; Strain K; Lo YC; Yuspa SH. 2000. The epidermal growth factor receptor is required to maintain the proliferative population in the basal compartment of epidermal tumors Cancer Res 60(13):3328-32. [PubMed: 10910032]  [MGI Ref ID J:63567]

Hayakawa-Yano Y; Nishida K; Fukami S; Gotoh Y; Hirano T; Nakagawa T; Shimazaki T; Okano H. 2007. Epidermal growth factor signaling mediated by grb2 associated binder1 is required for the spatiotemporally regulated proliferation of olig2-expressing progenitors in the embryonic spinal cord. Stem Cells 25(6):1410-22. [PubMed: 17332510]  [MGI Ref ID J:123565]

Jackson LF; Qiu TH; Sunnarborg SW; Chang A; Zhang C; Patterson C; Lee DC. 2003. Defective valvulogenesis in HB-EGF and TACE-null mice is associated with aberrant BMP signaling. EMBO J 22(11):2704-16. [PubMed: 12773386]  [MGI Ref ID J:83820]

Liu B; Xia X; Zhu F; Park E; Carbajal S; Kiguchi K; DiGiovanni J; Fischer SM; Hu Y. 2008. IKKalpha is required to maintain skin homeostasis and prevent skin cancer. Cancer Cell 14(3):212-25. [PubMed: 18772111]  [MGI Ref ID J:141162]

Repertinger SK; Campagnaro E; Fuhrman J; El-Abaseri T; Yuspa SH; Hansen LA. 2004. EGFR enhances early healing after cutaneous incisional wounding. J Invest Dermatol 123(5):982-9. [PubMed: 15482488]  [MGI Ref ID J:120140]

Schneider MR; Werner S; Paus R; Wolf E. 2008. Beyond wavy hairs: the epidermal growth factor receptor and its ligands in skin biology and pathology. Am J Pathol 173(1):14-24. [PubMed: 18556782]  [MGI Ref ID J:137366]

Strunk KE; Amann V; Threadgill DW. 2004. Phenotypic variation resulting from a deficiency of epidermal growth factor receptor in mice is caused by extensive genetic heterogeneity that can be genetically and molecularly partitioned. Genetics 167(4):1821-32. [PubMed: 15342520]  [MGI Ref ID J:92345]

Sun H; Oakley B. 2002. Development of anterior gustatory epithelia in the palate and tongue requires epidermal growth factor receptor. Dev Biol 242(1):31-43. [PubMed: 11795938]  [MGI Ref ID J:74312]

Wiesen JF; Young P; Werb Z; Cunha GR. 1999. Signaling through the stromal epidermal growth factor receptor is necessary for mammary ductal development. Development 126(2):335-44. [PubMed: 9847247]  [MGI Ref ID J:51436]

Yamaoka T; Yan F; Cao H; Hobbs SS; Dise RS; Tong W; Polk DB. 2008. Transactivation of EGF receptor and ErbB2 protects intestinal epithelial cells from TNF-induced apoptosis. Proc Natl Acad Sci U S A 105(33):11772-7. [PubMed: 18701712]  [MGI Ref ID J:138989]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	This strain is maintained by mating heterozygous mice with normal wildtype siblings. The mutation has been put on several genetic backgrounds, each of which displays a different phenotype. It is maintained on both inbred 129 and outbred CD1 genetic backgrounds. Expected coat color from breeding:Albino
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. At least two mice that carry the mutation (if it is a mutant strain) will be provided. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotypes and genders are needed. IMPORTANT NOTE: The genotypes of the animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire for possible genotypes for this specific strain. Animals typically ship within 13 to 16 weeks from your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will typically ship within 25 weeks. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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.

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Ordering and Purchasing Information

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Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

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In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

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The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.