PUBLICATION
Deficiency of the Synaptic Adhesion Protein Leucine-Rich Repeat Transmembrane Protein 4 Like 1 Affects Anxiety and Aggression in Zebrafish
- Authors
- Tatzl, E., Petracco, G., Faimann, I., Balasso, M., Mooslechner, A.A., Bärnthaler, T., Rodriguez-Blanco, G., Reichmann, F.
- ID
- ZDB-PUB-250405-4
- Date
- 2025
- Source
- Acta physiologica (Oxford, England) 241: e70042e70042 (Journal)
- Registered Authors
- Keywords
- aggression, anxiety, leucine‐rich repeat transmembrane protein 4, neurotransmission, synaptic plasticity
- MeSH Terms
-
- Anxiety*/genetics
- Anxiety*/metabolism
- Brain/metabolism
- Animals
- Membrane Proteins*/deficiency
- Membrane Proteins*/genetics
- Membrane Proteins*/metabolism
- Aggression*/physiology
- Zebrafish
- Nerve Tissue Proteins*/deficiency
- Nerve Tissue Proteins*/genetics
- Nerve Tissue Proteins*/metabolism
- Social Behavior
- Behavior, Animal/physiology
- Zebrafish Proteins*/deficiency
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 40183503 Full text @ Acta Physiol. (Oxf).
Citation
Tatzl, E., Petracco, G., Faimann, I., Balasso, M., Mooslechner, A.A., Bärnthaler, T., Rodriguez-Blanco, G., Reichmann, F. (2025) Deficiency of the Synaptic Adhesion Protein Leucine-Rich Repeat Transmembrane Protein 4 Like 1 Affects Anxiety and Aggression in Zebrafish. Acta physiologica (Oxford, England). 241:e70042e70042.
Abstract
Aim Leucine-rich repeat transmembrane proteins (LRRTMs) are synaptic adhesion proteins that regulate synapse development and function. They interact transsynaptically with presynaptic binding partners to promote presynaptic differentiation. Polymorphisms of LRRTM4, one of the four members of this protein family, have been linked to multiple neuropsychiatric disorders and childhood aggression, but the underlying mechanisms and physiological function of LRRTM4 during behavior are currently unclear.
Methods To characterize the role of this gene for brain function, we combined a battery of behavioral assays with transcriptomic and metabolomic analyses, using zebrafish as a model system.
Results Our findings revealed that lrrtm4l1, a brain-specific zebrafish orthologue of human LRRTM4, exhibits a brain region-specific expression pattern similar to humans, with strong expression in the dorsal telencephalon, a brain area critical for regulating emotional-affective and social behavior. lrrtm4l1-/- zebrafish displayed heightened anxiety and reduced aggression, while locomotion and social behavior remained unaffected by the gene knockout. Transcriptomic analysis of the telencephalon identified over 100 differentially expressed genes between wild-type and mutant zebrafish and an enrichment of pathways related to synaptic plasticity and neuronal signaling. The brain metabolome of lrrtm4l1-/- zebrafish showed multiple alterations, particularly in the dopaminergic and adenosinergic neurotransmitter systems.
Conclusion These findings suggest that LRRTMs may have functions beyond their established role in excitatory synapse development, such as the regulation of neurotransmission and behavior. Targeting LRRTM4 therapeutically may thus be an interesting novel approach to alleviate excessive aggression or anxiety associated with a number of neuropsychiatric conditions.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping