Developmental delays and reduced pup ultrasonic vocalizations but normal sociability in mice lacking the postsynaptic cell adhesion protein neuroligin2

Wöhr, Markus; Silverman, Jill L.; Scattoni, María Luisa; Turner, Sarah M.; Harris, Monica J.; Saxena, Roheeni; Crawley, Jacqueline N.

doi:10.1016/j.bbr.2012.07.024

Cited by 111 publications

(101 citation statements)

References 127 publications

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“…Employing our 3-chambered social approach task, a simple yes-or-no assay for sociability [13], absence of sociability was reported in mice with mutations in genes including Shank3 [15,16], Cntnap2 [17], Pten [18], Tsc1 [19], En2 [20], Gabrb3 [21], Ube3a triplication [22], and oxytocin receptor knockouts [23]. Normal 3-chambered social approach appeared in mice with mutations in genes including oxytocin [24], Shank1 [25], Nlgn2 [26], Ephrin-A [27] and 16p11.2 deletion [28] Variable findings on social approach across laboratories and in mouse lines generated on different genetic backgrounds have been reported for mutations including Fmr1 [29,30], Nlgn3 [31][32][33][34], and Nlgn4 [35,36]. Social deficits on the 3-chambered sociability have been wellreplicated in 2 inbred strains of mice, BTBR [10,12,[37][38][39][40][41][42][43][44] and Balb/cJ [45,46].…”

Section: Discoveries Of Autism-relevant Behaviors In Mouse Modelsmentioning

confidence: 96%

Behavioral and Neuroanatomical Phenotypes in Mouse Models of Autism

2015

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In order to understand the consequences of the mutation on behavioral and biological phenotypes relevant to autism, mutations in many of the risk genes for autism spectrum disorder have been experimentally generated in mice. Here, we summarize behavioral outcomes and neuroanatomical abnormalities, with a focus on highresolution magnetic resonance imaging of postmortem mouse brains. Results are described from multiple mouse models of autism spectrum disorder and comorbid syndromes, including the 15q11-13, 16p11.2, 22q11.2, Cntnap2, Engrailed2, Fragile X, Integrinβ3, MET, Neurexin1a, Neuroligin3, Reelin, Rett, Shank3, Slc6a4, tuberous sclerosis, and Williams syndrome models, and inbred strains with strong autism-relevant behavioral phenotypes, including BTBR and BALB. Concomitant behavioral and neuroanatomical abnormalities can strengthen the interpretation of results from a mouse model, and may elevate the usefulness of the model system for therapeutic discovery.

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Section: Discoveries Of Autism-relevant Behaviors In Mouse Modelsmentioning

confidence: 96%

Behavioral and Neuroanatomical Phenotypes in Mouse Models of Autism

2015

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“…The investigation of ultrasonic vocalization (USV) deficits has been previously explored in various mouse models of neurological diseases, both in early development from postnatal day (PD) 2 to 14 (Lai et al, 2014; Roy, Watkins, & Heck, 2012; Scattoni, Gandhy, Ricceri, & Crawley, 2008; Wohr, Roullet, Hung, Sheng, & Crawley, 2011; Wohr et al, 2013) and in adulthood ranging from PD60 to 120 (Belagodu, Johnson, & Galvez, 2016; Rotschafer, Trujillo, Dansie, Ethell, & Razak, 2012; Wohr, Roullet, Hung, et al, 2011). Mouse pups begin emitting ultrasonic vocalizations (USVs) shortly after birth and continue, although at a reduced rate, throughout adulthood in response to specific situations.…”

Section: Introductionmentioning

confidence: 99%

Spectral and temporal properties of calls reveal deficits in ultrasonic vocalizations of adult Fmr1 knockout mice

Hodges

Nolan

Reynolds

et al. 2017

Behavioural Brain Research

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The Fmr1 knockout (KO) mouse has commonly been used to investigate communication impairments, one of the key diagnostic symptoms observed in Fragile X syndrome (FXS) and Autism spectrum disorder (ASD). Many studies have found alterations in ultrasonic vocalizations (USVs) in neonatal Fmr1 KO mice, however, there is limited research investigating whether these deficits continue into adulthood. In the present study, we examine differences in female urine-induced ultrasonic vocalizations, scent marking behavior, odor discrimination, and open field activity in adult male Fmr1 KO and wildtype (WT) mice. Overall, we found extensive alterations between genotypes in both spectral and temporal properties of ultrasonic vocalizations. There was no difference in the average number of calls emitted by both genotypes, however, Fmr1 KO mice emitted calls of a higher frequency, decreased amplitude, and shorter duration than WT mice. Spectrographic analyses revealed statistically significant differences between genotypes in the types of calls emitted. Contrastingly, we found no differences in scent marking behavior, a form of social communication, or in odor discrimination and activity levels of the mice. The results corroborate previous studies emphasizing the importance of qualitative differences observed in vocalization behavior of Fmr1 KO mice, rather than quantitative measurements such as number of calls emitted. Overall, the study confirms the presence of abnormalities in vocalization behavior in adult Fmr1 KO mice that we believe are consistent with communication deficits seen in the syndrome.

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“…The importance of NL2 for inhibitory synapse development is evidenced by a reduction in GABAergic and glycinergic, but not glutamatergic, miniature inhibitory postsynaptic current frequency and amplitude in genetically targeted neurons lacking NL2 (11). At the behavioral level, loss of NL2 enhanced anxiety-like behavior in dark/light and open field tests and reduced ultrasonic vocalization (16,17). Mechanistically, loss of NL2 reduced perisomatic clustering of gephyrin and GABA receptors (11) with no change in symmetric synapse density (16).…”

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confidence: 99%

A Combined Transgenic Proteomic Analysis and Regulated Trafficking of Neuroligin-2

Kang

Cassidy

et al. 2014

Journal of Biological Chemistry

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Background: Brain inhibitory synaptic connections present challenges for molecular identification and imaging. Results: Transgenic mice expressing tagged neuroligin-2 were used to identify associated complexes and image inhibitory synapses in multiple brain regions. Conclusion: Neuroligin-2-associated complexes are enriched in synaptic components, and neuroligin-2 undergoes regulated dynamin-dependent endocytosis and retromer association. Significance: New data and approaches are presented for brain inhibitory synapse proteomics and imaging.

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Developmental delays and reduced pup ultrasonic vocalizations but normal sociability in mice lacking the postsynaptic cell adhesion protein neuroligin2

Cited by 111 publications

References 127 publications

Behavioral and Neuroanatomical Phenotypes in Mouse Models of Autism

Behavioral and Neuroanatomical Phenotypes in Mouse Models of Autism

Spectral and temporal properties of calls reveal deficits in ultrasonic vocalizations of adult Fmr1 knockout mice

A Combined Transgenic Proteomic Analysis and Regulated Trafficking of Neuroligin-2

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