An evolutionary conserved role for anaplastic lymphoma kinase in behavioral responses to ethanol.
Anaplastic lymphoma kinase (Alk) is a gene expressed in the nervous system that encodes a receptor tyrosine kinase commonly known for its oncogenic function in various human cancers. We have determined that Alk is associated with altered behavioral responses to ethanol in the fruit fly Drosophila me...
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Public Library of Science (PLoS)
2011
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oai:doaj.org-article:a85a1905315e4389912e69a18a2d54522021-11-18T06:49:34ZAn evolutionary conserved role for anaplastic lymphoma kinase in behavioral responses to ethanol.1932-620310.1371/journal.pone.0022636https://doaj.org/article/a85a1905315e4389912e69a18a2d54522011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21799923/?tool=EBIhttps://doaj.org/toc/1932-6203Anaplastic lymphoma kinase (Alk) is a gene expressed in the nervous system that encodes a receptor tyrosine kinase commonly known for its oncogenic function in various human cancers. We have determined that Alk is associated with altered behavioral responses to ethanol in the fruit fly Drosophila melanogaster, in mice, and in humans. Mutant flies containing transposon insertions in dAlk demonstrate increased resistance to the sedating effect of ethanol. Database analyses revealed that Alk expression levels in the brains of recombinant inbred mice are negatively correlated with ethanol-induced ataxia and ethanol consumption. We therefore tested Alk gene knockout mice and found that they sedate longer in response to high doses of ethanol and consume more ethanol than wild-type mice. Finally, sequencing of human ALK led to the discovery of four polymorphisms associated with a low level of response to ethanol, an intermediate phenotype that is predictive of future alcohol use disorders (AUDs). These results suggest that Alk plays an evolutionary conserved role in ethanol-related behaviors. Moreover, ALK may be a novel candidate gene conferring risk for AUDs as well as a potential target for pharmacological intervention.Amy W LasekJana LimChristopher L KliethermesKaren H BergerGeoff JoslynGerry BrushLiquan XueMargaret RobertsonMonica S MooreKaren VranizanStephan W MorrisMarc A SchuckitRaymond L WhiteUlrike HeberleinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 7, p e22636 (2011) |
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DOAJ |
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DOAJ |
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EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Amy W Lasek Jana Lim Christopher L Kliethermes Karen H Berger Geoff Joslyn Gerry Brush Liquan Xue Margaret Robertson Monica S Moore Karen Vranizan Stephan W Morris Marc A Schuckit Raymond L White Ulrike Heberlein An evolutionary conserved role for anaplastic lymphoma kinase in behavioral responses to ethanol. |
| description |
Anaplastic lymphoma kinase (Alk) is a gene expressed in the nervous system that encodes a receptor tyrosine kinase commonly known for its oncogenic function in various human cancers. We have determined that Alk is associated with altered behavioral responses to ethanol in the fruit fly Drosophila melanogaster, in mice, and in humans. Mutant flies containing transposon insertions in dAlk demonstrate increased resistance to the sedating effect of ethanol. Database analyses revealed that Alk expression levels in the brains of recombinant inbred mice are negatively correlated with ethanol-induced ataxia and ethanol consumption. We therefore tested Alk gene knockout mice and found that they sedate longer in response to high doses of ethanol and consume more ethanol than wild-type mice. Finally, sequencing of human ALK led to the discovery of four polymorphisms associated with a low level of response to ethanol, an intermediate phenotype that is predictive of future alcohol use disorders (AUDs). These results suggest that Alk plays an evolutionary conserved role in ethanol-related behaviors. Moreover, ALK may be a novel candidate gene conferring risk for AUDs as well as a potential target for pharmacological intervention. |
| format |
article |
| author |
Amy W Lasek Jana Lim Christopher L Kliethermes Karen H Berger Geoff Joslyn Gerry Brush Liquan Xue Margaret Robertson Monica S Moore Karen Vranizan Stephan W Morris Marc A Schuckit Raymond L White Ulrike Heberlein |
| author_facet |
Amy W Lasek Jana Lim Christopher L Kliethermes Karen H Berger Geoff Joslyn Gerry Brush Liquan Xue Margaret Robertson Monica S Moore Karen Vranizan Stephan W Morris Marc A Schuckit Raymond L White Ulrike Heberlein |
| author_sort |
Amy W Lasek |
| title |
An evolutionary conserved role for anaplastic lymphoma kinase in behavioral responses to ethanol. |
| title_short |
An evolutionary conserved role for anaplastic lymphoma kinase in behavioral responses to ethanol. |
| title_full |
An evolutionary conserved role for anaplastic lymphoma kinase in behavioral responses to ethanol. |
| title_fullStr |
An evolutionary conserved role for anaplastic lymphoma kinase in behavioral responses to ethanol. |
| title_full_unstemmed |
An evolutionary conserved role for anaplastic lymphoma kinase in behavioral responses to ethanol. |
| title_sort |
evolutionary conserved role for anaplastic lymphoma kinase in behavioral responses to ethanol. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/a85a1905315e4389912e69a18a2d5452 |
| work_keys_str_mv |
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