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Open Access Short paper

Wildtype epidermal growth factor receptor (Egfr) is not required for daily locomotor or masking behavior in mice

Reade B Roberts1, Carol L Thompson2, Daekee Lee1, Richard W Mankinen1, Aziz Sancar2 and David W Threadgill1*

Author Affiliations

1 Department of Genetics, CB 7264, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA

2 Department of Biochemistry, CB 7260, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA

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Journal of Circadian Rhythms 2006, 4:15  doi:10.1186/1740-3391-4-15

Published: 16 November 2006

Abstract

Background

Recent studies have implicated the epidermal growth factor receptor (EGFR) within the subparaventricular zone as being a major mediator of locomotor and masking behaviors in mice. The results were based on small cohorts of mice homozygous for the hypomorphic Egfrwa2 allele on a mixed, genetically uncontrolled background, and on intraventricular infusion of exogenous EGFR ligands. Subsequenlty, a larger study using the same genetically mixed background failed to replicate the original findings. Since both previous approaches were susceptible to experimental artifacts related to an uncontrolled genetic background, we analyzed the locomotor behaviors in Egfrwa2 mutant mice on genetically defined, congenic backgrounds.

Methods

Mice carrying the Egfrwa2 hypomorphic allele were bred to congenicity by backcrossing greater than ten generations onto C57BL/6J and 129S1/SvImJ genetic backgrounds. Homozygous Egfrwa2 mutant and wildtype littermates were evaluated for defects in locomotor and masking behaviors.

Results

Mice homozygous for Egfrwa2 showed normal daily locomotor activity and masking indistinguishable from wildtype littermates at two light intensities (200–300 lux and 400–500 lux).

Conclusion

Our results demonstrate that reduced EGFR activity alone is insufficient to perturb locomotor and masking behaviors in mice. Our results also suggest that other uncontrolled genetic or environmental parameters confounded previous experiments linking EGFR activity to daily locomotor activity and provide a cautionary tale for genetically uncontrolled studies.