Journal
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
Volume 100, Issue 3, Pages 566-574Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pbb.2011.10.024
Keywords
Anaplastic Lymphoma Kinase; Lymphocyte Tyrosine Kinase; Hippocampus; Spatial memory; Adult neurogenesis
Funding
- NCI [R01 CA69129]
- American Lebanese Syrian Associated Charities (ALSAC)
- St. Jude Children's Research Hospital
- NATIONAL CANCER INSTITUTE [R01CA069129] Funding Source: NIH RePORTER
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Anaplastic Lymphoma Kinase (Alk) is a receptor tyrosine kinase expressed throughout the adult mammalian hippocampus. Recent studies in Drosophila and prior studies in Caenorhabditis elegans have implicated Alk signaling in learning and neurogenesis. We have studied the roles of Alk and the closely related receptor Leukocyte Tyrosine Kinase (Ltk) in learning, behavior and neurogenesis. In the hippocampus, both receptors are expressed throughout the dentate gyrus, CA1 and CA3. To assess the functional roles of Alk and Ltk in the mammalian brain, we analyzed phenotypes in Alk mutant, Ltk mutant and Alk/Ltk double-mutant mice compared to wild-type littermates. Similar to Drosophila, we found enhanced performance in spatial memory in Alk mutant mice. Also similar to Drosophila, we observed reduced neurogenesis associated with loss of Alk function. We also report genetic interactions between Alk and Ltk with respect to neurogenesis and behavioral measures such as activity, anxiety levels, and retention of spatial memory. (C) 2011 Elsevier Inc. All rights reserved.
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