title: Impaired spatial memory and altered dendritic spine morphology in angiotensin II type 2 receptor-deficient mice.
abstract: Mental retardation is the most frequent cause of serious handicap in children and young adults. Mutations in the human angiotensin II type 2 receptor (AT2) have been implicated in X-linked forms of mental retardation. We here demonstrate that mice lacking the AT2 receptor gene are significantly impaired in their performance in a spatial memory task and in a one-way active avoidance task. As no difference was observed between the genotypes in fear conditioning, the detected deficit in spatial memory may not relate to fear. Notably, receptor knockout mice showed increased motility in an activity meter and elevated plus maze. Importantly, these mice are characterized by abnormal dendritic spine morphology and length, both features also found to be associated with some cases of mental retardation. These findings suggest a crucial role of AT2 in normal brain function and that dysfunction of the receptor has impact on brain development and ultrastructural morphology with distinct consequences on learning and memory.
authors.affiliation: Leibniz-Institut für Molekulare Pharmakologie, Berlin, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Maul
authors.forename: Oliver
authors.initials: O
authors.lastname: von Bohlen und Halbach
authors.forename: Axel
authors.initials: A
authors.lastname: Becker
authors.forename: Anja
authors.initials: A
authors.lastname: Sterner-Kock
authors.forename: Jörg-Peter
authors.initials: JP
authors.lastname: Voigt
authors.forename: Wolf-Eberhard
authors.initials: WE
authors.lastname: Siems
authors.forename: Gisela
authors.initials: G
authors.lastname: Grecksch
authors.forename: Thomas
authors.initials: T
authors.lastname: Walther
mesh_terms: D000818:Animals; D001362:Avoidance Learning; D049229:Dendritic Spines / Q000473:pathology* / Q000648:ultrastructure; D006624:Hippocampus / Q000648:ultrastructure; D008297:Male; D008569:Memory Disorders / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D044139:Receptor, Angiotensin, Type 2 / Q000172:deficiency* / Q000378:metabolism
chemical_list: D044139:Receptor, Angiotensin, Type 2