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UNCOVERING A BRAIN FUNCTION FOR AMOTL1: A NOVEL SEX-DEPENDENT MOUSE MODEL OF BIPOLAR DISORDER
Anthony Kischeland 10 co-authors
PORT - Łukasiewicz
FENS Forum 2026 (2026)
Barcelona, Spain
Board PS02-07PM-274
Presentation
Date TBA
Board: PS02-07PM-274
Event Information
Poster Board
PS02-07PM-274
Poster
View posterAbstract
Bipolar disorder is a complex neuropsychiatric illness marked by alternating manic and depressive episodes, yet its underlying mechanisms remain poorly understood. Although existing animal models capture certain mania-like features, more accurate models are needed to advance understanding of disease pathophysiology. The angiomotin family (AMOT, AMOTL1, AMOTL2) is known to regulate angiogenesis by organizing tight junctions and establishing cell polarity. However, only a few studies limited to AMOT have reported functions in the central nervous system, including roles in dendritic spine development and dendritic arborization. We will present evidence that systemic deletion of AMOTL1 leads to a spectrum of abnormalities characteristic for mouse models of bipolar disorder. AMOTL1 knockout (AL1 KO) males exhibit core mania-like behaviors, including locomotor hyperactivity, increased risk-taking, heightened sensitivity to low-dose of D-amphetamine, excessive circling and turning, and episodes of backward walking. These phenotypes were replicated in two complementary neuron-specific conditional knockout lines. Neurochemical analyses revealed dysregulated dopamine and serotonin levels across multiple brain regions, along with impaired glutamatergic transmission. Interestingly, AL1 KO females displayed increased anxiety-like and despair-like behaviors, indicating a sex-dependent divergence in phenotypes, with males predominantly exhibiting mania-like traits and females showing depressive-like features. This study demonstrates for the first time a functional role for AMOTL1 in the brain and strengthens the emerging view that angiomotins play important roles in the CNS. By recapitulating key behavioral, neurochemical, and sex-specific features of bipolar disorder, our novel mouse model provides a valuable tool for investigating disease mechanisms and testing potential therapeutic strategies.
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