Expression, subcellular localization, and mechanistic analysis of intellectual disability syndrome protein ABBA

A missense mutation in the MTSS2 gene, which encodes the I-BAR domain protein ABBA (Mtss1l/Mtss2), has been linked to an intellectual disability syndrome. To better understand the MTSS2 mutation-related effect in the brain, we elucidated the cells expressing ABBA and the localization of ABBA in these cells to get insights into which cells and processes might be dysfunctional in mutation-carrying patients. As a novel discovery, we found that ABBA was highly expressed in GABAergic inhibitory neurons, such as parvalbumin-positive interneurons in the hippocampus. At the subcellular level, ABBA localizes to the edges of membrane protrusions in various cells in the brain, suggesting a role in cell migration and spinogenesis. Overexpression of ABBA in pyramidal excitatory and inhibitory neurons increased dendritic spine density. Through live-cell imaging, we demonstrated that ABBA facilitates spine initiation by clustering on the plasma membrane before a new filopodium appears. However, our li..., Animals In the present study, we have used wild-type and transgenic Tg(Thy1-EGFP)MJrs/J mice (Jackson Laboratory) on a C57Bl/6J background. Tg(Thy1-EGFP)MJrs/J mice express EGFP in sparse subsets of neurons within specific populations. All experimental procedures were carried out according to Finnish laws and ethics under the EU directive 2010/63/EU (licenses: ESAVI/7404/2021, ESAVI/30031/2024, and GMO 3/S/12). Animals were kept in cages as groups of 2-4 mice in a controlled environment (temperature 21±1°C, humidity 50±10%, light period 06:00 AM to 6:00 PM) and supplied with food and water ad libitum. For tissue collection, animals were deeply anesthetized with pentobarbital solution (200 mg/kg) containing lidocaine and transcardially perfused using cold PBS. The brains were dissected and kept in 4% PFA for 24 hours and then cryoprotected in 20% sucrose solution for at least 48 hours before cryo-sectioning. The Thy1-GFP brains were cut sagittally into 50 µm sections with a cryostat (Lei..., # Data from: Expression, subcellular localization, and mechanistic analysis of intellectual disability syndrome protein ABBA Dataset DOI: [10.5061/dryad.ttdz08m8g](10.5061/dryad.ttdz08m8g) ## Description of the data and file structure ### Files and variables ``` Title of Dataset ``` Expression, subcellular localization, and mechanistic analysis of Intellectual disability syndrome protein ABBA Dataset DOI: [10.5061/dryad.ttdz08m8g](applewebdata://53C9C7CE-7FDF-4E59-8945-B1955748EB01/10.5061/dryad.ttdz08m8g) ``` Brief summary of dataset contents, contextualized in experimental procedures and results: ``` Data used for article Jabeen A, Khanal P, Toissalo E, Lahti L, Minkeviciene R, Kramm A, Rivera C, Hotulainen P. Expression, Subcellular Localization, and Mechanistic Analysis of Intellectual Disability Syndrome Protein ABBA. Mol Neurobiol. 2025 Dec 8;63(1):271. doi: 10.1007/s12035-025-05475-3. PMID: 41359239. Link to article: [https://link.springer.com/article/10.1007/s12035-025...,