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Comprehensive Behavioral Phenotyping of a 16p11.2 Del Mouse Model for Neurodevelopmental Disorders / Joseph F. 3rd LYNCH in Autism Research, 13-10 (October 2020)
[article]
Titre : Comprehensive Behavioral Phenotyping of a 16p11.2 Del Mouse Model for Neurodevelopmental Disorders Type de document : Texte imprimé et/ou numérique Auteurs : Joseph F. 3rd LYNCH, Auteur ; Sarah L. FERRI, Auteur ; Christopher C. ANGELAKOS, Auteur ; Hannah SCHOCH, Auteur ; Thomas NICKL-JOCKSCHAT, Auteur ; Arnold GONZALEZ, Auteur ; William Timothy O'BRIEN, Auteur ; Ted ABEL, Auteur Article en page(s) : p.1670-1684 Langues : Anglais (eng) Mots-clés : 16p11.2 autism spectrum disorders behavior copy number variant mouse model neurodevelopmental disorders phenotype Index. décimale : PER Périodiques Résumé : The microdeletion of copy number variant 16p11.2 is one of the most common genetic mutations associated with neurodevelopmental disorders, such as Autism Spectrum Disorders (ASDs). Here, we describe our comprehensive behavioral phenotyping of the 16p11.2 deletion line developed by Alea Mills on a C57BL/6J and 129S1/SvImJ F1 background (Del(m) ). Male and female Del(m) mice were tested in developmental milestones as preweanlings (PND2-PND12), and were tested in open field activity, elevated zero maze, rotarod, novel object recognition, fear conditioning, social approach, and other measures during post-weaning (PND21), adolescence (PND42), and adulthood (>PND70). Developmentally, Del(m) mice show distinct weight reduction that persists into adulthood. Del(m) males also have reduced grasp reflexes and limb strength during development, but no other reflexive deficits whereas Del(m) females show limb strength deficits and decreased sensitivity to heat. In a modified version of a rotarod task that measures balance and coordinated motor activity, Del(m) males, but not females, show improved performance at high speeds. Del(m) males and females also show age-specific reductions in anxiety-like behavior compared with WTs, but neither sex show deficits in a social preference task. When assessing learning and memory, Del(m) males and females show age-specific impairments in a novel object or spatial object recognition, but no deficits in contextual fear memory. This work extends the understanding of the behavioral phenotypes seen with 16p11.2 deletion by emphasizing age and sex-specific deficits; important variables to consider when studying mouse models for neurodevelopmental disorders. LAY SUMMARY: Autism spectrum disorder is a common neurodevelopmental disorder that causes repetitive behavior and impairments in social interaction and communication. Here, we assess the effects of one of the most common genetic alterations in ASDs, a deletion of one copy of 29 genes, using a mouse model. These animals show differences in behavior between males and females and across ages compared with control animals, including changes in development, cognition, and motor coordination. Autism Res 2020, 13: 1670-1684. © 2020 International Society for Autism Research and Wiley Periodicals LLC. En ligne : http://dx.doi.org/10.1002/aur.2357 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=431
in Autism Research > 13-10 (October 2020) . - p.1670-1684[article] Comprehensive Behavioral Phenotyping of a 16p11.2 Del Mouse Model for Neurodevelopmental Disorders [Texte imprimé et/ou numérique] / Joseph F. 3rd LYNCH, Auteur ; Sarah L. FERRI, Auteur ; Christopher C. ANGELAKOS, Auteur ; Hannah SCHOCH, Auteur ; Thomas NICKL-JOCKSCHAT, Auteur ; Arnold GONZALEZ, Auteur ; William Timothy O'BRIEN, Auteur ; Ted ABEL, Auteur . - p.1670-1684.
Langues : Anglais (eng)
in Autism Research > 13-10 (October 2020) . - p.1670-1684
Mots-clés : 16p11.2 autism spectrum disorders behavior copy number variant mouse model neurodevelopmental disorders phenotype Index. décimale : PER Périodiques Résumé : The microdeletion of copy number variant 16p11.2 is one of the most common genetic mutations associated with neurodevelopmental disorders, such as Autism Spectrum Disorders (ASDs). Here, we describe our comprehensive behavioral phenotyping of the 16p11.2 deletion line developed by Alea Mills on a C57BL/6J and 129S1/SvImJ F1 background (Del(m) ). Male and female Del(m) mice were tested in developmental milestones as preweanlings (PND2-PND12), and were tested in open field activity, elevated zero maze, rotarod, novel object recognition, fear conditioning, social approach, and other measures during post-weaning (PND21), adolescence (PND42), and adulthood (>PND70). Developmentally, Del(m) mice show distinct weight reduction that persists into adulthood. Del(m) males also have reduced grasp reflexes and limb strength during development, but no other reflexive deficits whereas Del(m) females show limb strength deficits and decreased sensitivity to heat. In a modified version of a rotarod task that measures balance and coordinated motor activity, Del(m) males, but not females, show improved performance at high speeds. Del(m) males and females also show age-specific reductions in anxiety-like behavior compared with WTs, but neither sex show deficits in a social preference task. When assessing learning and memory, Del(m) males and females show age-specific impairments in a novel object or spatial object recognition, but no deficits in contextual fear memory. This work extends the understanding of the behavioral phenotypes seen with 16p11.2 deletion by emphasizing age and sex-specific deficits; important variables to consider when studying mouse models for neurodevelopmental disorders. LAY SUMMARY: Autism spectrum disorder is a common neurodevelopmental disorder that causes repetitive behavior and impairments in social interaction and communication. Here, we assess the effects of one of the most common genetic alterations in ASDs, a deletion of one copy of 29 genes, using a mouse model. These animals show differences in behavior between males and females and across ages compared with control animals, including changes in development, cognition, and motor coordination. Autism Res 2020, 13: 1670-1684. © 2020 International Society for Autism Research and Wiley Periodicals LLC. En ligne : http://dx.doi.org/10.1002/aur.2357 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=431 Modulation of mu attenuation to social stimuli in children and adults with 16p11.2 deletions and duplications / C. M. HUDAC in Journal of Neurodevelopmental Disorders, 7-1 (December 2015)
[article]
Titre : Modulation of mu attenuation to social stimuli in children and adults with 16p11.2 deletions and duplications Type de document : Texte imprimé et/ou numérique Auteurs : C. M. HUDAC, Auteur ; A. KRESSE, Auteur ; Benjamin AARONSON, Auteur ; Trent D. DESCHAMPS, Auteur ; S. J. WEBB, Auteur ; Raphael BERNIER, Auteur Article en page(s) : p.25 Langues : Anglais (eng) Mots-clés : 16p11.2 Autism spectrum disorder (ASD) Copy number variation (CNV) Electroencephalogram (EEG) Molecular subtyping Mu attenuation Social perception Index. décimale : PER Périodiques Résumé : BACKGROUND: Copy number variations (CNV) within the recurrent ~600 kb chromosomal locus of 16p11.2 are associated with a wide range of neurodevelopmental disorders, including autism spectrum disorder (ASD). However, little is known about the social brain phenotype of 16p11.2 CNV and how this phenotype is related to the social impairments associated with CNVs at this locus. The aim of this preliminary study was to use molecular subtyping to establish the social brain phenotype of individuals with 16p11.2 CNV and how these patterns relate to typical development and ASD. METHODS: We evaluated the social brain phenotype as expressed by mu attenuation in 48 children and adults characterized as duplication carriers (n = 12), deletion carriers (n = 12), individuals with idiopathic ASD (n = 8), and neurotypical controls (n = 16). Participants watched videos containing social and nonsocial motion during electroencephalogram (EEG) acquisition. RESULTS: Overall, only the typical group exhibited predicted patterns of mu modulation to social information (e.g., greater mu attenuation for social than nonsocial motion). Both 16p11.2 CNV groups exhibited more mu attenuation for nonsocial than social motion. The ASD group did not discriminate between conditions and demonstrated less mu attenuation compared to the typical and duplication carriers. Single-trial analysis indicated that mu attenuation decreased over time more rapidly for 16p11.2 CNV groups than the typical group. The duplication group did not diverge from typical patterns of mu attenuation until after initial exposure. CONCLUSIONS: These results indicate atypical but unique patterns of mu attenuation for deletion and duplication carriers, highlighting the need to continue characterizing the social brain phenotype associated with 16p11.2 CNVs. En ligne : http://dx.doi.org/10.1186/s11689-015-9118-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=347
in Journal of Neurodevelopmental Disorders > 7-1 (December 2015) . - p.25[article] Modulation of mu attenuation to social stimuli in children and adults with 16p11.2 deletions and duplications [Texte imprimé et/ou numérique] / C. M. HUDAC, Auteur ; A. KRESSE, Auteur ; Benjamin AARONSON, Auteur ; Trent D. DESCHAMPS, Auteur ; S. J. WEBB, Auteur ; Raphael BERNIER, Auteur . - p.25.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 7-1 (December 2015) . - p.25
Mots-clés : 16p11.2 Autism spectrum disorder (ASD) Copy number variation (CNV) Electroencephalogram (EEG) Molecular subtyping Mu attenuation Social perception Index. décimale : PER Périodiques Résumé : BACKGROUND: Copy number variations (CNV) within the recurrent ~600 kb chromosomal locus of 16p11.2 are associated with a wide range of neurodevelopmental disorders, including autism spectrum disorder (ASD). However, little is known about the social brain phenotype of 16p11.2 CNV and how this phenotype is related to the social impairments associated with CNVs at this locus. The aim of this preliminary study was to use molecular subtyping to establish the social brain phenotype of individuals with 16p11.2 CNV and how these patterns relate to typical development and ASD. METHODS: We evaluated the social brain phenotype as expressed by mu attenuation in 48 children and adults characterized as duplication carriers (n = 12), deletion carriers (n = 12), individuals with idiopathic ASD (n = 8), and neurotypical controls (n = 16). Participants watched videos containing social and nonsocial motion during electroencephalogram (EEG) acquisition. RESULTS: Overall, only the typical group exhibited predicted patterns of mu modulation to social information (e.g., greater mu attenuation for social than nonsocial motion). Both 16p11.2 CNV groups exhibited more mu attenuation for nonsocial than social motion. The ASD group did not discriminate between conditions and demonstrated less mu attenuation compared to the typical and duplication carriers. Single-trial analysis indicated that mu attenuation decreased over time more rapidly for 16p11.2 CNV groups than the typical group. The duplication group did not diverge from typical patterns of mu attenuation until after initial exposure. CONCLUSIONS: These results indicate atypical but unique patterns of mu attenuation for deletion and duplication carriers, highlighting the need to continue characterizing the social brain phenotype associated with 16p11.2 CNVs. En ligne : http://dx.doi.org/10.1186/s11689-015-9118-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=347 Quantitative gait assessment in children with 16p11.2 syndrome / S. GOLDMAN in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)
[article]
Titre : Quantitative gait assessment in children with 16p11.2 syndrome Type de document : Texte imprimé et/ou numérique Auteurs : S. GOLDMAN, Auteur ; A. K. MCCULLOUGH, Auteur ; S. D. YOUNG, Auteur ; C. MUELLER, Auteur ; A. STAHL, Auteur ; A. ZOELLER, Auteur ; L. D. ABBRUZZESE, Auteur ; A. K. RAO, Auteur ; J. MONTES, Auteur Article en page(s) : 26 p. Langues : Anglais (eng) Mots-clés : 16p11.2 Autism spectrum disorder Children Gait Motor function Neurodevelopment disorder Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurodevelopmental disorders such as 16p11.2 syndrome are frequently associated with motor impairments including locomotion. The lack of precise measures of gait, combined with the challenges inherent in studying children with neurodevelopmental disorders, hinders quantitative motor assessments. Gait and balance are quantifiable measures that may help to refine the motor phenotype in 16p11.2. The characterization of motor profile is useful to study the trajectories of locomotion performance of children with genetic variants and may provide insights into neural pathway dysfunction based on genotype/phenotype model. METHODS: Thirty-six children (21 probands with 16p11.2 deletion and duplication mutation and 15 unaffected siblings), with a mean age of 8.5 years (range 3.2-15.4) and 55% male, were enrolled. Of the probands, 23% (n = 6) had a confirmed diagnosis of autism spectrum disorder (ASD) and were all male. Gait assessments included 6-min walk test (6MWT), 10-m walk/run test (10MWR), timed-up-and-go test (TUG), and spatio-temporal measurements of preferred- and fast-paced walking. The Pediatric Evaluation of Disability Inventory-Computer Adaptive Tests (PEDI-CAT), a caregiver-reported functional assessment, was administered. Measures of balance were calculated using percent time in double support and base of support. Analyses of the six children with ASD were described separately. RESULTS: Thirty-six participants completed the protocol. Compared with sibling controls, probands had significantly lower scores on the 6MWT (p = 0.04), 10MWR (p = 0.01), and TUG (p = 0.005). Group differences were also identified in base of support (p = 0.003). Probands had significantly lower PEDI-CAT scores in all domains including the mobility scale (p < 0.001). Using age-matched subsamples, the ASD and non-ASD genetic variant groups had larger base of support compared to the controls. In the fast-paced condition, all participants increased their velocity, and there was a corresponding decrease in percent time in double support compared to the preferred-pace condition in all participants. Only the ASD group presented with upper limb arm/hand stereotypies. CONCLUSIONS: Children with 16p11.2, with and without ASD, present with balance impairment during locomotion activities. Probands performed worse on functional assessments, and quantitative measures revealed differences in base of support. These results highlight the importance of using precise measures to differentiate motor dysfunction in children with neurodevelopmental disorders. En ligne : https://dx.doi.org/10.1186/s11689-019-9286-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409
in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 26 p.[article] Quantitative gait assessment in children with 16p11.2 syndrome [Texte imprimé et/ou numérique] / S. GOLDMAN, Auteur ; A. K. MCCULLOUGH, Auteur ; S. D. YOUNG, Auteur ; C. MUELLER, Auteur ; A. STAHL, Auteur ; A. ZOELLER, Auteur ; L. D. ABBRUZZESE, Auteur ; A. K. RAO, Auteur ; J. MONTES, Auteur . - 26 p.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 26 p.
Mots-clés : 16p11.2 Autism spectrum disorder Children Gait Motor function Neurodevelopment disorder Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurodevelopmental disorders such as 16p11.2 syndrome are frequently associated with motor impairments including locomotion. The lack of precise measures of gait, combined with the challenges inherent in studying children with neurodevelopmental disorders, hinders quantitative motor assessments. Gait and balance are quantifiable measures that may help to refine the motor phenotype in 16p11.2. The characterization of motor profile is useful to study the trajectories of locomotion performance of children with genetic variants and may provide insights into neural pathway dysfunction based on genotype/phenotype model. METHODS: Thirty-six children (21 probands with 16p11.2 deletion and duplication mutation and 15 unaffected siblings), with a mean age of 8.5 years (range 3.2-15.4) and 55% male, were enrolled. Of the probands, 23% (n = 6) had a confirmed diagnosis of autism spectrum disorder (ASD) and were all male. Gait assessments included 6-min walk test (6MWT), 10-m walk/run test (10MWR), timed-up-and-go test (TUG), and spatio-temporal measurements of preferred- and fast-paced walking. The Pediatric Evaluation of Disability Inventory-Computer Adaptive Tests (PEDI-CAT), a caregiver-reported functional assessment, was administered. Measures of balance were calculated using percent time in double support and base of support. Analyses of the six children with ASD were described separately. RESULTS: Thirty-six participants completed the protocol. Compared with sibling controls, probands had significantly lower scores on the 6MWT (p = 0.04), 10MWR (p = 0.01), and TUG (p = 0.005). Group differences were also identified in base of support (p = 0.003). Probands had significantly lower PEDI-CAT scores in all domains including the mobility scale (p < 0.001). Using age-matched subsamples, the ASD and non-ASD genetic variant groups had larger base of support compared to the controls. In the fast-paced condition, all participants increased their velocity, and there was a corresponding decrease in percent time in double support compared to the preferred-pace condition in all participants. Only the ASD group presented with upper limb arm/hand stereotypies. CONCLUSIONS: Children with 16p11.2, with and without ASD, present with balance impairment during locomotion activities. Probands performed worse on functional assessments, and quantitative measures revealed differences in base of support. These results highlight the importance of using precise measures to differentiate motor dysfunction in children with neurodevelopmental disorders. En ligne : https://dx.doi.org/10.1186/s11689-019-9286-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 Loss of the Chr16p11.2 ASD candidate gene QPRT leads to aberrant neuronal differentiation in the SH-SY5Y neuronal cell model / D. HASLINGER in Molecular Autism, 9 (2018)
[article]
Titre : Loss of the Chr16p11.2 ASD candidate gene QPRT leads to aberrant neuronal differentiation in the SH-SY5Y neuronal cell model Type de document : Texte imprimé et/ou numérique Auteurs : D. HASLINGER, Auteur ; R. WALTES, Auteur ; A. YOUSAF, Auteur ; S. LINDLAR, Auteur ; I. SCHNEIDER, Auteur ; C. K. LIM, Auteur ; M. M. TSAI, Auteur ; B. K. GARVALOV, Auteur ; A. ACKER-PALMER, Auteur ; N. KREZDORN, Auteur ; B. ROTTER, Auteur ; T. ACKER, Auteur ; G. J. GUILLEMIN, Auteur ; S. FULDA, Auteur ; C. M. FREITAG, Auteur ; Andreas G. CHIOCCHETTI, Auteur Article en page(s) : 56p. Langues : Anglais (eng) Mots-clés : 16p11.2 Autism CRISPR/Cas9 Kynurenine Quinolinate phosphoribosyltransferase Quinolinic acid Sholl analysis has been positively reviewed by the ethic's committee Frankfurt (No 267/09).All authors agree to publish the presented work.All authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Altered neuronal development is discussed as the underlying pathogenic mechanism of autism spectrum disorders (ASD). Copy number variations of 16p11.2 have recurrently been identified in individuals with ASD. Of the 29 genes within this region, quinolinate phosphoribosyltransferase (QPRT) showed the strongest regulation during neuronal differentiation of SH-SY5Y neuroblastoma cells. We hypothesized a causal relation between this tryptophan metabolism-related enzyme and neuronal differentiation. We thus analyzed the effect of QPRT on the differentiation of SH-SY5Y and specifically focused on neuronal morphology, metabolites of the tryptophan pathway, and the neurodevelopmental transcriptome. Methods: The gene dosage-dependent change of QPRT expression following Chr16p11.2 deletion was investigated in a lymphoblastoid cell line (LCL) of a deletion carrier and compared to his non-carrier parents. Expression of QPRT was tested for correlation with neuromorphology in SH-SY5Y cells. QPRT function was inhibited in SH-SY5Y neuroblastoma cells using (i) siRNA knockdown (KD), (ii) chemical mimicking of loss of QPRT, and (iii) complete CRISPR/Cas9-mediated knock out (KO). QPRT-KD cells underwent morphological analysis. Chemically inhibited and QPRT-KO cells were characterized using viability assays. Additionally, QPRT-KO cells underwent metabolite and whole transcriptome analyses. Genes differentially expressed upon KO of QPRT were tested for enrichment in biological processes and co-regulated gene-networks of the human brain. Results: QPRT expression was reduced in the LCL of the deletion carrier and significantly correlated with the neuritic complexity of SH-SY5Y. The reduction of QPRT altered neuronal morphology of differentiated SH-SY5Y cells. Chemical inhibition as well as complete KO of the gene were lethal upon induction of neuronal differentiation, but not proliferation. The QPRT-associated tryptophan pathway was not affected by KO. At the transcriptome level, genes linked to neurodevelopmental processes and synaptic structures were affected. Differentially regulated genes were enriched for ASD candidates, and co-regulated gene networks were implicated in the development of the dorsolateral prefrontal cortex, the hippocampus, and the amygdala. Conclusions: In this study, QPRT was causally related to in vitro neuronal differentiation of SH-SY5Y cells and affected the regulation of genes and gene networks previously implicated in ASD. Thus, our data suggest that QPRT may play an important role in the pathogenesis of ASD in Chr16p11.2 deletion carriers. En ligne : https://dx.doi.org/10.1186/s13229-018-0239-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371
in Molecular Autism > 9 (2018) . - 56p.[article] Loss of the Chr16p11.2 ASD candidate gene QPRT leads to aberrant neuronal differentiation in the SH-SY5Y neuronal cell model [Texte imprimé et/ou numérique] / D. HASLINGER, Auteur ; R. WALTES, Auteur ; A. YOUSAF, Auteur ; S. LINDLAR, Auteur ; I. SCHNEIDER, Auteur ; C. K. LIM, Auteur ; M. M. TSAI, Auteur ; B. K. GARVALOV, Auteur ; A. ACKER-PALMER, Auteur ; N. KREZDORN, Auteur ; B. ROTTER, Auteur ; T. ACKER, Auteur ; G. J. GUILLEMIN, Auteur ; S. FULDA, Auteur ; C. M. FREITAG, Auteur ; Andreas G. CHIOCCHETTI, Auteur . - 56p.
Langues : Anglais (eng)
in Molecular Autism > 9 (2018) . - 56p.
Mots-clés : 16p11.2 Autism CRISPR/Cas9 Kynurenine Quinolinate phosphoribosyltransferase Quinolinic acid Sholl analysis has been positively reviewed by the ethic's committee Frankfurt (No 267/09).All authors agree to publish the presented work.All authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Altered neuronal development is discussed as the underlying pathogenic mechanism of autism spectrum disorders (ASD). Copy number variations of 16p11.2 have recurrently been identified in individuals with ASD. Of the 29 genes within this region, quinolinate phosphoribosyltransferase (QPRT) showed the strongest regulation during neuronal differentiation of SH-SY5Y neuroblastoma cells. We hypothesized a causal relation between this tryptophan metabolism-related enzyme and neuronal differentiation. We thus analyzed the effect of QPRT on the differentiation of SH-SY5Y and specifically focused on neuronal morphology, metabolites of the tryptophan pathway, and the neurodevelopmental transcriptome. Methods: The gene dosage-dependent change of QPRT expression following Chr16p11.2 deletion was investigated in a lymphoblastoid cell line (LCL) of a deletion carrier and compared to his non-carrier parents. Expression of QPRT was tested for correlation with neuromorphology in SH-SY5Y cells. QPRT function was inhibited in SH-SY5Y neuroblastoma cells using (i) siRNA knockdown (KD), (ii) chemical mimicking of loss of QPRT, and (iii) complete CRISPR/Cas9-mediated knock out (KO). QPRT-KD cells underwent morphological analysis. Chemically inhibited and QPRT-KO cells were characterized using viability assays. Additionally, QPRT-KO cells underwent metabolite and whole transcriptome analyses. Genes differentially expressed upon KO of QPRT were tested for enrichment in biological processes and co-regulated gene-networks of the human brain. Results: QPRT expression was reduced in the LCL of the deletion carrier and significantly correlated with the neuritic complexity of SH-SY5Y. The reduction of QPRT altered neuronal morphology of differentiated SH-SY5Y cells. Chemical inhibition as well as complete KO of the gene were lethal upon induction of neuronal differentiation, but not proliferation. The QPRT-associated tryptophan pathway was not affected by KO. At the transcriptome level, genes linked to neurodevelopmental processes and synaptic structures were affected. Differentially regulated genes were enriched for ASD candidates, and co-regulated gene networks were implicated in the development of the dorsolateral prefrontal cortex, the hippocampus, and the amygdala. Conclusions: In this study, QPRT was causally related to in vitro neuronal differentiation of SH-SY5Y cells and affected the regulation of genes and gene networks previously implicated in ASD. Thus, our data suggest that QPRT may play an important role in the pathogenesis of ASD in Chr16p11.2 deletion carriers. En ligne : https://dx.doi.org/10.1186/s13229-018-0239-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371