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In vivo ablation of promyelocytic leukemia (PML) tumor suppressor protein leads to behavioral changes in mice
Author(s) -
Martinez Luis Alberto,
Tejada-Simon Maria Victoria
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb691
Subject(s) - neurogenesis , knockout mouse , morris water navigation task , conditional gene knockout , neuroscience , promyelocytic leukemia protein , hippocampus , synaptic plasticity , schaffer collateral , hippocampal formation , environmental enrichment , long term potentiation , psychology , biology , transcription factor , nuclear protein , receptor , phenotype , biochemistry , excitatory postsynaptic potential , gene , inhibitory postsynaptic potential
The promyelocytic leukemia protein (PML) is a tumor suppressor factor primarily known for its involvement in acute promyelocytic leukemia (APL). Prospective studies of PML in the brain are sparse. However, recent studies have provided evidence that in the central nervous system PML participates in neurogenesis. To further understand the role of PML in the mammalian brain, we studied plasticity and behavioral changes in a PML knockout mouse. If PML is involved in neurogenesis, an important process for proper brain development as well as learning and memory functions, we hypothesized that PML might have a role in plasticity and cognition by regulating neuronal development. Behavioral studies demonstrated that PML knockout mice present abnormalities in conditioned learning and spatial memory, as determined by fear conditioning and Morris water maze tasks, respectively. Additional behavior anomalies were revealed during tests which measure anxiety, with PML knockout mice exhibiting less anxiety, locomotion and hyperactivity. Finally, impairments in hippocampus‐dependent learning were mirrored by altered long‐term plasticity at Schaffer collateral‐CA1 synapses. Therefore, we provide evidence for a novel and important role of PML, beyond cell proliferation, where it contributes to synaptic plasticity and associated behavioral processes.