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Hillman, C; Petracco, G; Fontana, BD; Scaia, MF; Dalla-Vecchia, E; Wetton, JH; Norton, WHJ; Parker, MO; Reichmann, F.
Genetic disruption of leucine rich repeat transmembrane protein 4 like 1 induces a pro-social behavioural phenotype in zebrafish.
Neurobiol Dis. 2025; 107251 Doi: 10.1016/j.nbd.2025.107251
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Führende Autor*innen der Med Uni Graz
Reichmann Florian
Co-Autor*innen der Med Uni Graz
Petracco Giulia
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Abstract:
BACKGROUND: In humans, disruptions in social behaviour are characteristic of many neuropsychiatric disorders, where both genetic risk factors and synaptic dysfunctions can contribute to the phenotype. Among the genes implicated in synaptic regulation, the synaptic adhesion protein leucine-rich repeat transmembrane protein 4 (LRRTM4) has been identified as a key player in maintaining synaptic function and neuronal circuit integrity. However, the potential involvement of LRRTM4 in modulating social behaviour and its contribution to social deficits has yet to be explored. METHODS: In the current study, we used zebrafish to study how deficiency in lrrtm4l1, a zebrafish orthologue of LRRTM4, affects sociality. For this, the social behaviour of homozygous lrrtm4l1-/- mutant zebrafish was analysed in multiple behavioural assays and the brain transcriptome of mutant animals was investigated by RNAseq. RESULTS: Mutant zebrafish displayed a pro-social phenotype in multiple behavioural assays. Groups of lrrtm4l1-/- zebrafish formed more cohesive shoals and mutant individuals spent more time in the vicinity of conspecifics during a social interaction test. They were also less aggressive and in contrast to wild-type zebrafish did not differentiate in their interactions with known and unknown groups of fish. Neurotranscriptomic analysis revealed 560 differentially expressed genes including changes in glutamatergic neurotransmitter signalling, tryptophan-kynurenine metabolism and synaptic plasticity. CONCLUSION: These findings suggest that lrrtm4l1 is an important regulator of social behaviour in zebrafish. In a translational perspective, LRRTM4 is a promising potential therapeutic target that warrants further investigation in the framework of neuropsychiatric conditions characterized by major social impairments.

Find related publications in this database (Keywords)
Lrrtm4
Zebrafish
Social behaviour
Synaptic plasticity
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