Gene Symbol: Nlgn3
Description: neuroligin 3
Alias: A230085M13Rik, HNL3, NL3, NLG3, neuroligin-3, gliotactin homolog, neuroligin 3 protein
Species: mouse
Products:     Nlgn3

Top Publications

  1. Chih B, Engelman H, Scheiffele P. Control of excitatory and inhibitory synapse formation by neuroligins. Science. 2005;307:1324-8 pubmed
    ..Electrophysiological analysis revealed a predominant reduction of inhibitory synaptic function. Thus, neuroligins control the formation and functional balance of excitatory and inhibitory synapses in hippocampal neurons. ..
  2. Radyushkin K, Hammerschmidt K, Boretius S, Varoqueaux F, El Kordi A, Ronnenberg A, et al. Neuroligin-3-deficient mice: model of a monogenic heritable form of autism with an olfactory deficit. Genes Brain Behav. 2009;8:416-25 pubmed publisher
    ..Our findings show that the NL-3 knockout mouse represents a useful animal model for understanding pathophysiological events in monogenic heritable ASD and for developing novel treatment strategies in this devastating human disorder. ..
  3. Földy C, Malenka R, Sudhof T. Autism-associated neuroligin-3 mutations commonly disrupt tonic endocannabinoid signaling. Neuron. 2013;78:498-509 pubmed publisher
    ..Our data thus suggest that neuroligin-3 is specifically required for tonic endocannabinoid signaling, raising the possibility that alterations in endocannabinoid signaling may contribute to autism pathophysiology. ..
  4. Kolozsi E, MacKenzie R, Roullet F, deCatanzaro D, Foster J. Prenatal exposure to valproic acid leads to reduced expression of synaptic adhesion molecule neuroligin 3 in mice. Neuroscience. 2009;163:1201-10 pubmed publisher situ hybridization and analyzed with densitometry to examine expression of three NLGN genes (NLGN1, NLGN2, and NLGN3) and three NRXN genes (NRXN1, NRXN2, and NRXN3)...
  5. Varoqueaux F, Aramuni G, Rawson R, Mohrmann R, Missler M, Gottmann K, et al. Neuroligins determine synapse maturation and function. Neuron. 2006;51:741-54 pubmed
    ..Our data show that neuroligins are required for proper synapse maturation and brain function, but not for the initial formation of synaptic contacts. ..
  6. Tabuchi K, Blundell J, Etherton M, Hammer R, Liu X, Powell C, et al. A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice. Science. 2007;318:71-6 pubmed
    ..These data suggest that increased inhibitory synaptic transmission may contribute to human ASDs and that the R451C knockin mice may be a useful model for studying autism-related behaviors. ..
  7. Budreck E, Scheiffele P. Neuroligin-3 is a neuronal adhesion protein at GABAergic and glutamatergic synapses. Eur J Neurosci. 2007;26:1738-48 pubmed
    ..and GABAergic synapses, respectively, but the cellular expression and synaptic localization of the endogenous NL3 and NL4 isoforms are unknown...
  8. Jamain S, Radyushkin K, Hammerschmidt K, Granon S, Boretius S, Varoqueaux F, et al. Reduced social interaction and ultrasonic communication in a mouse model of monogenic heritable autism. Proc Natl Acad Sci U S A. 2008;105:1710-5 pubmed publisher
  9. Chadman K, Gong S, Scattoni M, Boltuck S, Gandhy S, Heintz N, et al. Minimal aberrant behavioral phenotypes of neuroligin-3 R451C knockin mice. Autism Res. 2008;1:147-58 pubmed publisher
    ..Mice with the human R451C mutation (NL3), identical to the point mutation found in two brothers with autism spectrum disorders, were generated and ..

More Information


  1. Cao W, Lin S, Xia Q, Du Y, Yang Q, Zhang M, et al. Gamma Oscillation Dysfunction in mPFC Leads to Social Deficits in Neuroligin 3 R451C Knockin Mice. Neuron. 2018;97:1253-1260.e7 pubmed publisher
    Neuroligins (NLs) are critical for synapse formation and function. NL3 R451C is an autism-associated mutation. NL3 R451C knockin (KI) mice exhibit autistic behavioral abnormalities, including social novelty deficits...
  2. Gilbert M, Smith J, Roskams A, Auld V. Neuroligin 3 is a vertebrate gliotactin expressed in the olfactory ensheathing glia, a growth-promoting class of macroglia. Glia. 2001;34:151-64 pubmed
    ..we have isolated a potential vertebrate gliotactin homologue from mice and rat and found that it corresponds to neuroligin 3. Using a combination of RT-PCR and immunohistochemistry, we have found that neuroligin 3 is expressed during ..
  3. Zhang B, Sudhof T. Neuroligins Are Selectively Essential for NMDAR Signaling in Cerebellar Stellate Interneurons. J Neurosci. 2016;36:9070-83 pubmed publisher
    ..Our results reveal a critical and selective role for neuroligins in the regulation of NMDAR responses in cerebellar stellate interneurons. ..
  4. Rothwell P, Fuccillo M, Maxeiner S, Hayton S, Gokce O, Lim B, et al. Autism-associated neuroligin-3 mutations commonly impair striatal circuits to boost repetitive behaviors. Cell. 2014;158:198-212 pubmed publisher
  5. Schwartzer J, Koenig C, Berman R. Using mouse models of autism spectrum disorders to study the neurotoxicology of gene-environment interactions. Neurotoxicol Teratol. 2013;36:17-35 pubmed publisher
  6. Kumar D, Thakur M. Age-related expression of Neurexin1 and Neuroligin3 is correlated with presynaptic density in the cerebral cortex and hippocampus of male mice. Age (Dordr). 2015;37:17 pubmed publisher
    Neurexin1 (Nrxn1) and Neuroligin3 (Nlgn3) are cell adhesion proteins, which play an important role in synaptic plasticity that declines with advancing age. However, the expression of these proteins during aging has not been analyzed...
  7. Hill Yardin E, Argyropoulos A, Hosie S, Rind G, Anderson P, Hannan A, et al. Reduced susceptibility to induced seizures in the Neuroligin-3(R451C) mouse model of autism. Neurosci Lett. 2015;589:57-61 pubmed publisher
    ..In order to determine whether a point mutation in the gene for the synaptic protein, Neuroligin-3 (Nlgn3, R451C), identified in patients with ASD alters seizure susceptibility, we administered the proconvulsant ..
  8. Kalbassi S, Bachmann S, Cross E, Roberton V, Baudouin S. Male and Female Mice Lacking Neuroligin-3 Modify the Behavior of Their Wild-Type Littermates. Eneuro. 2017;4: pubmed publisher
    ..Here we explore the possibility that mixed-group housing of mice carrying a deletion of Nlgn3, a gene associated with autism spectrum disorders, and their wild-type littermates induces changes in each ..
  9. Gutierrez R, Hung J, Zhang Y, Kertesz A, Espina F, Colicos M. Altered synchrony and connectivity in neuronal networks expressing an autism-related mutation of neuroligin 3. Neuroscience. 2009;162:208-21 pubmed publisher
    ..Here we show how the expression of autism-associated neuroligin mutation R471C-NL3 affects synchrony in dissociated cultures of rat hippocampal neurons...
  10. Burrows E, Eastwood A, May C, Kolbe S, Hill T, McLachlan N, et al. Social Isolation Alters Social and Mating Behavior in the R451C Neuroligin Mouse Model of Autism. Neural Plast. 2017;2017:8361290 pubmed publisher
    ..The Neuroligin-3 (NL3) mouse, expressing a R451C mutation discovered in two Swedish brothers with ASD, exhibits impaired social ..
  11. Cellot G, Cherubini E. Reduced inhibitory gate in the barrel cortex of Neuroligin3R451C knock-in mice, an animal model of autism spectrum disorders. Physiol Rep. 2014;2: pubmed publisher
    ..One of these, the R451C mutation of the gene encoding for Neuroligin3 (Nlgn3), has been found in patients with familial forms of ASDs...
  12. Kumar D, Thakur M. Perinatal exposure to bisphenol-A impairs spatial memory through upregulation of neurexin1 and neuroligin3 expression in male mouse brain. PLoS ONE. 2014;9:e110482 pubmed publisher
    ..the effect of perinatal exposure to BPA on the expression of synaptic proteins neurexin1 (Nrxn1) and neuroligin3 (Nlgn3), dendritic spine density and spatial memory in postnatal male mice...
  13. Steadman P, Ellegood J, Szulc K, Turnbull D, Joyner A, Henkelman R, et al. Genetic effects on cerebellar structure across mouse models of autism using a magnetic resonance imaging atlas. Autism Res. 2014;7:124-37 pubmed publisher
    ..These imaging results are discussed in relation to repetitive behaviors, sociability, and learning in the context of autism. This work further illuminates the cerebellum's role in autism. ..
  14. Hoon M, Krishnamoorthy V, Gollisch T, Falkenburger B, Varoqueaux F. Loss of Neuroligin3 specifically downregulates retinal GABAA?2 receptors without abolishing direction selectivity. PLoS ONE. 2017;12:e0181011 pubmed publisher
    ..In this study we show that NL3 is also predominantly expressed at inhibitory postsynapses in the retinal inner plexiform layer (IPL), where it ..
  15. Crawley J. Translational animal models of autism and neurodevelopmental disorders. Dialogues Clin Neurosci. 2012;14:293-305 pubmed
    ..The field is now poised to employ the most robust phenotypes in the most replicable mouse models for preclinical screening of novel therapeutics. ..
  16. Chanda S, Marro S, Wernig M, Sudhof T. Neurons generated by direct conversion of fibroblasts reproduce synaptic phenotype caused by autism-associated neuroligin-3 mutation. Proc Natl Acad Sci U S A. 2013;110:16622-7 pubmed publisher
    ..Our data show that the effect of the R704C mutation is applicable even to neurons transdifferentiated from fibroblasts and constitute a proof-of-concept demonstration that iN cells can be used for cellular disease modeling. ..
  17. Baudouin S, Gaudias J, Gerharz S, Hatstatt L, Zhou K, Punnakkal P, et al. Shared synaptic pathophysiology in syndromic and nonsyndromic rodent models of autism. Science. 2012;338:128-32 pubmed publisher
    ..These phenotypes could be rescued by reexpression of neuroligin-3 in juvenile mice, highlighting the possibility of reverting neuronal circuit alterations in autism after the completion of development. ..
  18. Chanda S, Hale W, Zhang B, Wernig M, Sudhof T. Unique versus Redundant Functions of Neuroligin Genes in Shaping Excitatory and Inhibitory Synapse Properties. J Neurosci. 2017;37:6816-6836 pubmed publisher
    ..e., NL1, NL2, and NL3), either individually or in combinations, in cultured mouse hippocampal and cortical neurons...
  19. Heupel K, Sargsyan V, Plomp J, Rickmann M, Varoqueaux F, Zhang W, et al. Loss of transforming growth factor-beta 2 leads to impairment of central synapse function. Neural Dev. 2008;3:25 pubmed publisher
    ..The functional alterations in the respiratory center of the brain are probably the underlying cause of the perinatal death of the TGF-beta2 knock-out mice. ..
  20. Zhang B, Chen L, Liu X, Maxeiner S, Lee S, Gokce O, et al. Neuroligins Sculpt Cerebellar Purkinje-Cell Circuits by Differential Control of Distinct Classes of Synapses. Neuron. 2015;87:781-96 pubmed publisher
    ..Using systematic analyses of all neuroligins in a defined neural circuit, our data thus show that neuroligins differentially contribute to various Purkinje-cell synapses in the cerebellum in vivo. ..
  21. Gobert R, Joubert L, Curchod M, Salvat C, Foucault I, Jorand Lebrun C, et al. Convergent functional genomics of oligodendrocyte differentiation identifies multiple autoinhibitory signaling circuits. Mol Cell Biol. 2009;29:1538-53 pubmed publisher
    ..Oligodendrocytic differentiation feedback loops may therefore yield pharmacological targets to treat disease related to dysfunctional myelin deposition. ..
  22. Poulopoulos A, Soykan T, Tuffy L, Hammer M, Varoqueaux F, Brose N. Homodimerization and isoform-specific heterodimerization of neuroligins. Biochem J. 2012;446:321-30 pubmed publisher
    ..we identified differences in the dimerization capacity of autism-associated neuroligin mutants, and found that neuroligin 3 R471C mutants can form heterodimers with neuroligin 1...
  23. Etherton M, Földy C, Sharma M, Tabuchi K, Liu X, Shamloo M, et al. Autism-linked neuroligin-3 R451C mutation differentially alters hippocampal and cortical synaptic function. Proc Natl Acad Sci U S A. 2011;108:13764-9 pubmed publisher
    ..genes were identified in patients with familial autism, including the R451C substitution in neuroligin-3 (NL3)...
  24. Etherton M, Tabuchi K, Sharma M, Ko J, Sudhof T. An autism-associated point mutation in the neuroligin cytoplasmic tail selectively impairs AMPA receptor-mediated synaptic transmission in hippocampus. EMBO J. 2011;30:2908-19 pubmed publisher
    ..Our results suggest that the cytoplasmic tail of neuroligin-3 has a central role in synaptic transmission by modulating the recruitment of AMPA receptors to postsynaptic sites at excitatory synapses. ..
  25. Sato Y, Suzuki S, Iijima Y, Iijima T. Neuroligin-induced presynaptic differentiation through SLM2-mediated splicing modifications of neurexin in cerebellar cultures. Biochem Biophys Res Commun. 2017;493:1030-1036 pubmed publisher
    ..Therefore, our findings may provide further insights into NRX-NL mediated synapse specification. ..
  26. Tanaka K, Ahmari S, Leonardo E, Richardson Jones J, Budreck E, Scheiffele P, et al. Flexible Accelerated STOP Tetracycline Operator-knockin (FAST): a versatile and efficient new gene modulating system. Biol Psychiatry. 2010;67:770-3 pubmed publisher
    ..demonstrate the flexibility and broad applicability of the FAST system by targeting several genes encoding proteins implicated in neuropsychiatric disorders: Mlc1, neuroligin 3, the serotonin 1A receptor, and the serotonin 1B receptor.
  27. Polepalli J, Wu H, Goswami D, Halpern C, Südhof T, Malenka R. Modulation of excitation on parvalbumin interneurons by neuroligin-3 regulates the hippocampal network. Nat Neurosci. 2017;20:219-229 pubmed publisher
  28. Olsen O, Moore K, Fukata M, Kazuta T, Trinidad J, Kauer F, et al. Neurotransmitter release regulated by a MALS-liprin-alpha presynaptic complex. J Cell Biol. 2005;170:1127-34 pubmed
    ..These findings are consistent with a model whereby the MALS-CASK-liprin-alpha complex recruits components of the synaptic release machinery to adhesive proteins of the active zone. ..
  29. de la Torre Ubieta L, Won H, Stein J, Geschwind D. Advancing the understanding of autism disease mechanisms through genetics. Nat Med. 2016;22:345-61 pubmed publisher
    ..Despite the challenges, these advances provide a solid foundation for the development of rational, targeted molecular therapies. ..
  30. Kumar M, Duda J, Hwang W, Kenworthy C, Ittyerah R, Pickup S, et al. High resolution magnetic resonance imaging for characterization of the neuroligin-3 knock-in mouse model associated with autism spectrum disorder. PLoS ONE. 2014;9:e109872 pubmed publisher
    ..The volumetric and DTI studies aid in understanding the biology of disrupting function on an ASD risk model and may assist in the development of imaging biomarkers for ASD. ..
  31. JARAMILLO T, Liu S, Pettersen A, Birnbaum S, Powell C. Autism-related neuroligin-3 mutation alters social behavior and spatial learning. Autism Res. 2014;7:264-72 pubmed publisher
  32. Karvat G, Kimchi T. Systematic autistic-like behavioral phenotyping of 4 mouse strains using a novel wheel-running assay. Behav Brain Res. 2012;233:405-14 pubmed publisher the new behavioral paradigm; 2 control lines (C57BL/6 and ICR) and 2 mouse-models of autism (BTBR T+ tf/J and Nlgn3(tm1Sud))...
  33. Speed H, Masiulis I, Gibson J, Powell C. Increased Cortical Inhibition in Autism-Linked Neuroligin-3R451C Mice Is Due in Part to Loss of Endocannabinoid Signaling. PLoS ONE. 2015;10:e0140638 pubmed publisher
    ..inherited, X-linked point mutation leading to an arginine to cysteine substitution at amino acid 451 (R451C) of Neuroligin 3 (NLGN3R451C) is a likely cause of autism in two brothers...
  34. Zhang B, Seigneur E, Wei P, Gokce O, Morgan J, Sudhof T. Developmental plasticity shapes synaptic phenotypes of autism-associated neuroligin-3 mutations in the calyx of Held. Mol Psychiatry. 2017;22:1483-1491 pubmed publisher
    ..Thus, although acute manipulations more likely reveal basic gene functions, developmental plasticity can be a major factor in shaping the overall phenotypes of genetic neuropsychiatric disorders. ..
  35. Kazdoba T, Leach P, Crawley J. Behavioral phenotypes of genetic mouse models of autism. Genes Brain Behav. 2016;15:7-26 pubmed publisher
    ..Robust, replicated autism-relevant behavioral outcomes in a genetic mouse model lend credence to a causal role for specific gene contributions and downstream biological mechanisms in the etiology of autism. ..
  36. Liu J, Grace K, Horner R, Cortez M, Shao Y, Jia Z. Neuroligin 3 R451C mutation alters electroencephalography spectral activity in an animal model of autism spectrum disorders. Mol Brain. 2017;10:10 pubmed publisher
    ..Following the identification of Nlgn3R451C mutation in patients with ASD, its effects on synaptic transmission and social behaviours have ..
  37. Heller E, Zhang W, Selimi F, Earnheart J, Slimak M, Santos Torres J, et al. The biochemical anatomy of cortical inhibitory synapses. PLoS ONE. 2012;7:e39572 pubmed publisher
  38. Tanabe Y, Naito Y, Vasuta C, Lee A, Soumounou Y, Linhoff M, et al. IgSF21 promotes differentiation of inhibitory synapses via binding to neurexin2?. Nat Commun. 2017;8:408 pubmed publisher
    ..Here the authors show that IgSF21 interacts with neurexin2? to induce presynaptic differentiation of inhibitory synapses, and that mice lacking IgSF21 exhibit deficits in inhibitory synaptic transmission. ..
  39. Divya T, Lalitha S, Parvathy S, Subashini C, Sanalkumar R, Dhanesh S, et al. Regulation of Tlx3 by Pax6 is required for the restricted expression of Chrnα3 in Cerebellar Granule Neuron progenitors during development. Sci Rep. 2016;6:30337 pubmed publisher
  40. Ko J, Soler Llavina G, Fuccillo M, Malenka R, Sudhof T. Neuroligins/LRRTMs prevent activity- and Ca2+/calmodulin-dependent synapse elimination in cultured neurons. J Cell Biol. 2011;194:323-34 pubmed publisher
  41. Fischer J, Hammerschmidt K. Ultrasonic vocalizations in mouse models for speech and socio-cognitive disorders: insights into the evolution of vocal communication. Genes Brain Behav. 2011;10:17-27 pubmed publisher
    ..The precise nature as well as the interaction of these factors is yet to be determined. ..