Impaired passive avoidance learning in mice lacking central neuronal nicotinic acetylcholine receptors
Section snippets
Mice
α7 And β2 null mutant mice were previously generated from 129/SvEv ES cells (Orr-Urtreger et al., 1997; Xu et al., 1999) and backcrossed eight times onto a C57Bl/6 background. α7β2 Double null mutant mice were generated by crossing α7−/− mice with β2−/− mice. The resulting α7±β2± mice were interbred and α7±β2+/+ or α7±β2−/− progeny were interbred. The resulting α7+/+β2+/+ or α7−/−β2−/− mice were interbred to produce test animals. Tail biopsies were taken after weaning at 3–6 weeks of age and
Results
Mice lacking both α7 nAChRs and the β2 nAChRs were generated by breeding mice with single mutations previously described (Orr-Urtreger et al., 1997; Xu et al., 1999). Double mutant mice α7−/−β2−/− were similar in weight and appearance to their wild-type, age-matched controls and could not be distinguished without genotyping using PCR (data not shown). Mice were evaluated on a battery of behavioral tests (see McIlwain et al., 2001), which included assays for locomotor activity, anxiety, motor
Discussion
We generated mice which lack the majority of nAChRs in the CNS. Mutant α7−/−β2−/− mice appeared normal in their home cage; however, they differed significantly from α7+/+β2+/+ mice in a number of ways when tested using various behavioral paradigms. Mutant α7−/−β2−/− made significantly more transitions in the light–dark test. However, the overall exploratory behavior in the open-field was similar between α7−/−β2−/− and wildtype mice. Together these data indicate that mutant α7−/−β2−/− are less
Acknowledgments
The authors wish to thank Dr. Arthur Beaudet, MD, for providing the mouse models and for support and Dr. Amir Fayyazuddin, PhD, for useful discussions and critical reading of the manuscript. The work was supported by NIDA PO1 DA12661. The authors are particularly grateful to Leah Goldberg for outstanding technical assistance.
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