Brain abnormalities in a Neuroligin3 R451C knockin mouse model associated with autism / Jacob ELLEGOOD in Autism Research, 4-5 (October 2011)  

Public ISBD [article]  inAutism Research > 4-5 (October 2011) . - p.368-376 Titre : Brain abnormalities in a Neuroligin3 R451C knockin mouse model associated with autism Type de document : Texte imprimé et/ou numérique Auteurs : Jacob ELLEGOOD, Auteur ; Jason LERCH, Auteur ; R. Mark HENKELMAN, Auteur Année de publication : 2011 Article en page(s) : p.368-376 Langues : Anglais (eng) Mots-clés : animal models  magnetic resonance imaging  diffusion tensor imaging  neuroligin3  volume assessment Index. décimale : PER Périodiques Résumé : Magnetic resonance imaging (MRI) has been used quite extensively for examining morphological changes in human and animal brains. One of the many advantages to examining mouse models of human autism is that we are able to examine single gene targets, like that of Neuroligin3 R451C knockin (NL3 KI), which has been directly implicated in human autism. The NL3 KI mouse model has marked volume differences in many different structures in the brain: gray matter structures, such as the hippocampus, the striatum, and the thalamus, were all found to be smaller in the NL3 KI. Further, many white matter structures were found to be significantly smaller, such as the cerebral peduncle, corpus callosum, fornix/fimbria, and internal capsule. Fractional anisotropy measurements in these structures were also measured, and no differences were found. The volume changes in the white matter regions, therefore, are not due to a general breakdown in the microstructure of the tissue and seem to be caused by fewer axons or less mature axons. A larger radial diffusivity was also found in localized regions of the corpus callosum and cerebellum. The corpus callosal changes are particularly interesting as the thinning (or reduced volume) of the corpus callosum is a consistent finding in autism. This suggests that the NL3 KI model may be useful for examining white matter changes associated with autism. Autism Res2011,4:368–376. © 2011 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.215 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=145 [article] Brain abnormalities in a Neuroligin3 R451C knockin mouse model associated with autism [Texte imprimé et/ou numérique] / Jacob ELLEGOOD, Auteur ; Jason LERCH, Auteur ; R. Mark HENKELMAN, Auteur . - 2011 . - p.368-376. Langues : Anglais (eng) in Autism Research > 4-5 (October 2011) . - p.368-376 Mots-clés : animal models  magnetic resonance imaging  diffusion tensor imaging  neuroligin3  volume assessment Index. décimale : PER Périodiques Résumé : Magnetic resonance imaging (MRI) has been used quite extensively for examining morphological changes in human and animal brains. One of the many advantages to examining mouse models of human autism is that we are able to examine single gene targets, like that of Neuroligin3 R451C knockin (NL3 KI), which has been directly implicated in human autism. The NL3 KI mouse model has marked volume differences in many different structures in the brain: gray matter structures, such as the hippocampus, the striatum, and the thalamus, were all found to be smaller in the NL3 KI. Further, many white matter structures were found to be significantly smaller, such as the cerebral peduncle, corpus callosum, fornix/fimbria, and internal capsule. Fractional anisotropy measurements in these structures were also measured, and no differences were found. The volume changes in the white matter regions, therefore, are not due to a general breakdown in the microstructure of the tissue and seem to be caused by fewer axons or less mature axons. A larger radial diffusivity was also found in localized regions of the corpus callosum and cerebellum. The corpus callosal changes are particularly interesting as the thinning (or reduced volume) of the corpus callosum is a consistent finding in autism. This suggests that the NL3 KI model may be useful for examining white matter changes associated with autism. Autism Res2011,4:368–376. © 2011 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.215 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=145

Genetic Effects on Cerebellar Structure Across Mouse Models of Autism Using a Magnetic Resonance Imaging Atlas / Patrick E. STEADMAN in Autism Research, 7-1 (February 2014)  

Public ISBD [article]  inAutism Research > 7-1 (February 2014) . - p.124-137 Titre : Genetic Effects on Cerebellar Structure Across Mouse Models of Autism Using a Magnetic Resonance Imaging Atlas Type de document : Texte imprimé et/ou numérique Auteurs : Patrick E. STEADMAN, Auteur ; Jacob ELLEGOOD, Auteur ; Kamila U. SZULC, Auteur ; Daniel H. TURNBULL, Auteur ; Alexandra L. JOYNER, Auteur ; R. Mark HENKELMAN, Auteur ; Jason LERCH, Auteur Article en page(s) : p.124-137 Langues : Anglais (eng) Mots-clés : animal models  neuroimaging  neuroanatomy  structural MRI  genetics Index. décimale : PER Périodiques Résumé : Magnetic resonance imaging (MRI) of autism populations is confounded by the inherent heterogeneity in the individuals' genetics and environment, two factors difficult to control for. Imaging genetic animal models that recapitulate a mutation associated with autism quantify the impact of genetics on brain morphology and mitigate the confounding factors in human studies. Here, we used MRI to image three genetic mouse models with single mutations implicated in autism: Neuroligin-3 R451C knock-in, Methyl-CpG binding protein-2 (MECP2) 308-truncation and integrin ?3 homozygous knockout. This study identified the morphological differences specific to the cerebellum, a structure repeatedly linked to autism in human neuroimaging and postmortem studies. To accomplish a comparative analysis, a segmented cerebellum template was created and used to segment each study image. This template delineated 39 different cerebellar structures. For Neuroligin-3 R451C male mutants, the gray (effect size (ES)?=?1.94, FDR q?=?0.03) and white (ES?=?1.84, q?=?0.037) matter of crus II lobule and the gray matter of the paraflocculus (ES?=?1.45, q?=?0.045) were larger in volume. The MECP2 mutant mice had cerebellar volume changes that increased in scope depending on the genotype: hemizygous males to homozygous females. The integrin ?3 mutant mouse had a drastically smaller cerebellum than controls with 28 out of 39 cerebellar structures smaller. 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. En ligne : http://dx.doi.org/10.1002/aur.1344 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227 [article] Genetic Effects on Cerebellar Structure Across Mouse Models of Autism Using a Magnetic Resonance Imaging Atlas [Texte imprimé et/ou numérique] / Patrick E. STEADMAN, Auteur ; Jacob ELLEGOOD, Auteur ; Kamila U. SZULC, Auteur ; Daniel H. TURNBULL, Auteur ; Alexandra L. JOYNER, Auteur ; R. Mark HENKELMAN, Auteur ; Jason LERCH, Auteur . - p.124-137. Langues : Anglais (eng) in Autism Research > 7-1 (February 2014) . - p.124-137 Mots-clés : animal models  neuroimaging  neuroanatomy  structural MRI  genetics Index. décimale : PER Périodiques Résumé : Magnetic resonance imaging (MRI) of autism populations is confounded by the inherent heterogeneity in the individuals' genetics and environment, two factors difficult to control for. Imaging genetic animal models that recapitulate a mutation associated with autism quantify the impact of genetics on brain morphology and mitigate the confounding factors in human studies. Here, we used MRI to image three genetic mouse models with single mutations implicated in autism: Neuroligin-3 R451C knock-in, Methyl-CpG binding protein-2 (MECP2) 308-truncation and integrin ?3 homozygous knockout. This study identified the morphological differences specific to the cerebellum, a structure repeatedly linked to autism in human neuroimaging and postmortem studies. To accomplish a comparative analysis, a segmented cerebellum template was created and used to segment each study image. This template delineated 39 different cerebellar structures. For Neuroligin-3 R451C male mutants, the gray (effect size (ES)?=?1.94, FDR q?=?0.03) and white (ES?=?1.84, q?=?0.037) matter of crus II lobule and the gray matter of the paraflocculus (ES?=?1.45, q?=?0.045) were larger in volume. The MECP2 mutant mice had cerebellar volume changes that increased in scope depending on the genotype: hemizygous males to homozygous females. The integrin ?3 mutant mouse had a drastically smaller cerebellum than controls with 28 out of 39 cerebellar structures smaller. 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. En ligne : http://dx.doi.org/10.1002/aur.1344 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227

Magnetic Resonance Imaging as a Tool for the Study of Mouse Models of Autism / Jacob ELLEGOOD in Autism - Open Access, 2-S ([01/12/2012])  

Public ISBD [article]  inAutism - Open Access > 2-S [01/12/2012] . - 8 p. Titre : Magnetic Resonance Imaging as a Tool for the Study of Mouse Models of Autism Type de document : Texte imprimé et/ou numérique Auteurs : Jacob ELLEGOOD, Auteur ; R. Mark HENKELMAN, Auteur ; Jason P. LERCH, Auteur Article en page(s) : 8 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Autism is a heterogeneous disorder, in both its behaviour and genetics. This heterogeneity has led to inconsistencies in the neuroanatomical findings in human autistic patients. The benefit of a model system, such as the mouse, is that there could be a decrease in the heterogeneity of the genetics and standardization of the environment could be done, in order to determine a specific anatomical phenotype, which is representative of a specific genotype. Magnetic Resonance Imaging (MRI) has been used quite extensively to examine morphological changes in the mouse brain; however, examining volume and tissue microstructure changes in mouse models of autism with MRI, is just in its infancy. This review will discuss the current research on anatomical phenotyping in mouse models of autism. En ligne : https://dx.doi.org/10.4172/2165-7890.S1-008 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Magnetic Resonance Imaging as a Tool for the Study of Mouse Models of Autism [Texte imprimé et/ou numérique] / Jacob ELLEGOOD, Auteur ; R. Mark HENKELMAN, Auteur ; Jason P. LERCH, Auteur . - 8 p. Langues : Anglais (eng) in Autism - Open Access > 2-S [01/12/2012] . - 8 p. Index. décimale : PER Périodiques Résumé : Autism is a heterogeneous disorder, in both its behaviour and genetics. This heterogeneity has led to inconsistencies in the neuroanatomical findings in human autistic patients. The benefit of a model system, such as the mouse, is that there could be a decrease in the heterogeneity of the genetics and standardization of the environment could be done, in order to determine a specific anatomical phenotype, which is representative of a specific genotype. Magnetic Resonance Imaging (MRI) has been used quite extensively to examine morphological changes in the mouse brain; however, examining volume and tissue microstructure changes in mouse models of autism with MRI, is just in its infancy. This review will discuss the current research on anatomical phenotyping in mouse models of autism. En ligne : https://dx.doi.org/10.4172/2165-7890.S1-008 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

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