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Generation and validation of mice carrying a conditional allele of the epidermal growth factor receptor.
Genesis. 2009 Feb; 47(2):85-92.G

Abstract

The epidermal growth factor receptor (EGFR) is important for normal homeostasis in a variety of tissues and, when abnormally expressed or mutated, contributes to the development of many diseases. However, in vivo functional studies are hindered by the lack of adult mice lacking EGFR because of the pre- and postnatal lethality of EGFR deficient mice. We generated a conditional allele of Egfr (Egfr(tm1Dwt)) by flanking exon 3 with loxP sites in order to investigate tissue-specific functions of this widely expressed receptor tyrosine kinase. The activity of the Egfr(tm1Dwt) allele is indistinguishable from wildtype Egfr. Conversely, the Egfr(Delta) allele, generated by Cre-mediated deletion of exon 3 using the germline EIIa-Cre transgenic line, functions as a null allele. Egfr(Delta/Delta) embryos that have complete ablation of EGFR activity and die at mid-gestation with placental defects identical to those reported for mice homozygous for the Egfr(tm1Mag) null allele. We also inactivated the Egfr(tm1Dwt) allele tissue-specifically in the skin epithelium using the K14-Cre transgenic line. These mice were viable but exhibited wavy coat hair remarkably similar to mice homozygous for the Egfr(wa2) hypomorphic allele or heterozygous for the Egfr(Wa5) antimorphic allele. These results suggest that the hairless phenotype of Egfr nullizygous mice is not solely due to absence of EGFR in the epithelium, but that EGFR activity is required also in skin stromal cells for normal hair morphogenesis. This new mouse model should have wide utility to inactivate Egfr conditionally for functional analysis of EGFR in adult tissues and disease states.

Authors+Show Affiliations

Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Validation Study

Language

eng

PubMed ID

19115345

Citation

Lee, Tang-Cheng, and David W. Threadgill. "Generation and Validation of Mice Carrying a Conditional Allele of the Epidermal Growth Factor Receptor." Genesis (New York, N.Y. : 2000), vol. 47, no. 2, 2009, pp. 85-92.
Lee TC, Threadgill DW. Generation and validation of mice carrying a conditional allele of the epidermal growth factor receptor. Genesis. 2009;47(2):85-92.
Lee, T. C., & Threadgill, D. W. (2009). Generation and validation of mice carrying a conditional allele of the epidermal growth factor receptor. Genesis (New York, N.Y. : 2000), 47(2), 85-92. https://doi.org/10.1002/dvg.20464
Lee TC, Threadgill DW. Generation and Validation of Mice Carrying a Conditional Allele of the Epidermal Growth Factor Receptor. Genesis. 2009;47(2):85-92. PubMed PMID: 19115345.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Generation and validation of mice carrying a conditional allele of the epidermal growth factor receptor. AU - Lee,Tang-Cheng, AU - Threadgill,David W, PY - 2008/12/31/entrez PY - 2008/12/31/pubmed PY - 2009/5/9/medline SP - 85 EP - 92 JF - Genesis (New York, N.Y. : 2000) JO - Genesis VL - 47 IS - 2 N2 - The epidermal growth factor receptor (EGFR) is important for normal homeostasis in a variety of tissues and, when abnormally expressed or mutated, contributes to the development of many diseases. However, in vivo functional studies are hindered by the lack of adult mice lacking EGFR because of the pre- and postnatal lethality of EGFR deficient mice. We generated a conditional allele of Egfr (Egfr(tm1Dwt)) by flanking exon 3 with loxP sites in order to investigate tissue-specific functions of this widely expressed receptor tyrosine kinase. The activity of the Egfr(tm1Dwt) allele is indistinguishable from wildtype Egfr. Conversely, the Egfr(Delta) allele, generated by Cre-mediated deletion of exon 3 using the germline EIIa-Cre transgenic line, functions as a null allele. Egfr(Delta/Delta) embryos that have complete ablation of EGFR activity and die at mid-gestation with placental defects identical to those reported for mice homozygous for the Egfr(tm1Mag) null allele. We also inactivated the Egfr(tm1Dwt) allele tissue-specifically in the skin epithelium using the K14-Cre transgenic line. These mice were viable but exhibited wavy coat hair remarkably similar to mice homozygous for the Egfr(wa2) hypomorphic allele or heterozygous for the Egfr(Wa5) antimorphic allele. These results suggest that the hairless phenotype of Egfr nullizygous mice is not solely due to absence of EGFR in the epithelium, but that EGFR activity is required also in skin stromal cells for normal hair morphogenesis. This new mouse model should have wide utility to inactivate Egfr conditionally for functional analysis of EGFR in adult tissues and disease states. SN - 1526-968X UR - https://www.unboundmedicine.com/medline/citation/19115345/Generation_and_validation_of_mice_carrying_a_conditional_allele_of_the_epidermal_growth_factor_receptor_ L2 - https://doi.org/10.1002/dvg.20464 DB - PRIME DP - Unbound Medicine ER -