Lack of adrenomedullin in the mouse brain results in behavioral changes, anxiety, and lower survival under stress conditions.

Proceedings of the National Academy of Sciences of the United States of America
A P FernándezAlfredo Martínez

Abstract

The adrenomedullin (AM) gene, adm, is widely expressed in the central nervous system (CNS) and several functions have been suggested for brain AM. Until now, a formal confirmation of these actions using genetic models has been elusive since the systemic adm knockout results in embryo lethality. We have built a conditional knockout mouse model using the Cre/loxP approach. When crossed with transgenic mice expressing the Cre recombinase under the tubulin Talpha-1 promoter, we obtained animals with no AM expression in the CNS but normal levels in other organs. These animals lead normal lives and do not present any gross morphological defect. Specific areas of the brain of animals lacking CNS AM contain hyperpolymerized tubulin, a consequence of AM downregulation. Behavioral analysis shows that mice with no AM in their brain have impaired motor coordination and are hyperactive and overanxious when compared to their wild-type littermates. Treatment with methylphenidate, haloperidol, and diazepam did not show differences between genotypes. Circulating levels of adrenocorticotropic hormone and corticosterone were similar in knockout and wild-type mice. Animals with no brain AM were less resistant to hypobaric hypoxia than wild-type mi...Continue Reading

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Citations

Feb 26, 2010·Cell and Tissue Research·Eva Vergaño-VeraAlfredo Martínez
Jul 3, 2010·Journal of Molecular Neuroscience : MN·Kazuhiro TakahashiKazuhito Totsune
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Jun 10, 2016·Histochemistry and Cell Biology·Josune García-SanmartínAlfredo Martínez
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Feb 16, 2012·Endocrinology·Ignacio M Larráyoz, Alfredo Martínez
Jan 10, 2018·Frontiers in Physiology·Sonia Martínez-HerreroAlfredo Martínez
Apr 28, 2017·Frontiers in Physiology·Rafael PeláezAlfredo Martínez
Jun 18, 2019·The Journal of Clinical Investigation·Andras IringStefan Offermanns
Jul 29, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Valentina ChiodiManlio Vinciguerra

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