Variations in post-perfusion immersion fixation and storage alter MRI measurements of mouse brain morphometry

Guzman, A. Elizabeth de; Wong, Michael D.; Gleave, Jacqueline A.; Nieman, Brian J.

doi:10.1016/j.neuroimage.2016.06.028

Cited by 76 publications

(63 citation statements)

References 31 publications

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“…After perfusion, mice were decapitated and the skin, lower jaw, ears, and the cartilaginous nose tip were removed. The brain and remaining skull structures were incubated in 4% paraformaldehyde + 2 mM ProHance overnight at 4°C, then transferred to 0.1 M PBS containing 2 mM ProHance and 0.02% sodium azide for at least 1 month before MRI scanning 32 .…”

Section: Methodsmentioning

confidence: 99%

Kctd13 deletion reduces synaptic transmission via increased RhoA

Escamilla

Filonova

Walker

et al. 2017

Nature

130

171

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Copy-number variants of chromosome 16 region 16p11.2 are linked to neuropsychiatric disorders1–6 and are among the most prevalent in autism spectrum disorders1,2,7. Of many 16p11.2 genes, Kctd13 has been implicated as a major driver of neurodevelopmental phenotypes8,9. The function of KCTD13 in the mammalian brain, however, remains unknown. Here we delete the Kctd13 gene in mice and demonstrate reduced synaptic transmission. Reduced synaptic transmission correlates with increased levels of Ras homolog gene family, member A (RhoA), a KCTD13/CUL3 ubiquitin ligase substrate, and is reversed by RhoA inhibition, suggesting increased RhoA as an important mechanism. In contrast to a previous knockdown study8, deletion of Kctd13 or kctd13 does not increase brain size or neurogenesis in mice or zebrafish, respectively. These findings implicate Kctd13 in the regulation of neuronal function relevant to neuropsychiatric disorders and clarify the role of Kctd13 in neurogenesis and brain size. Our data also reveal a potential role for RhoA as a therapeutic target in disorders associated with KCTD13 deletion.

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Section: Methodsmentioning

confidence: 99%

Kctd13 deletion reduces synaptic transmission via increased RhoA

Escamilla

Filonova

Walker

et al. 2017

Nature

130

171

View full text Add to dashboard Cite

show abstract

“…Perfusions were performed at a rate of approximately 60 ml/hr. After perfusion, the brain and remaining skull structures were incubated in 4% PFA + 2 mM ProHance overnight at 4°C and transferred to 0.1 M PBS containing 2 mM ProHance and 0.02% sodium azide for at least 1 month prior to MRI scanning (de Guzman, Wong, Gleave, & Nieman, 2016). A multi‐channel 7.0 Tesla MRI scanner (Agilent Inc., Palo Alto, CA) was used to image the brains within skulls.…”

Section: Methodsmentioning

confidence: 99%

Distinct cerebellar foliation anomalies in a CHD7 haploinsufficient mouse model of CHARGE syndrome

Whittaker

Kasah

Donovan

et al. 2017

American J of Med Genetics Pt C

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Mutations in the gene encoding the ATP dependent chromatin‐remodeling factor, CHD7 are the major cause of CHARGE (Coloboma, Heart defects, Atresia of the choanae, Retarded growth and development, Genital‐urinary anomalies, and Ear defects) syndrome. Neurodevelopmental defects and a range of neurological signs have been identified in individuals with CHARGE syndrome, including developmental delay, lack of coordination, intellectual disability, and autistic traits. We previously identified cerebellar vermis hypoplasia and abnormal cerebellar foliation in individuals with CHARGE syndrome. Here, we report mild cerebellar hypoplasia and distinct cerebellar foliation anomalies in a Chd7 haploinsufficient mouse model. We describe specific alterations in the precise spatio‐temporal sequence of fissure formation during perinatal cerebellar development responsible for these foliation anomalies. The altered cerebellar foliation pattern in Chd7 haploinsufficient mice show some similarities to those reported in mice with altered Engrailed, Fgf8 or Zic1 gene expression and we propose that mutations or polymorphisms in these genes may modify the cerebellar phenotype in CHARGE syndrome. Our findings in a mouse model of CHARGE syndrome indicate that a careful analysis of cerebellar foliation may be warranted in patients with CHARGE syndrome, particularly in patients with cerebellar hypoplasia and developmental delay.

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“…Briefly, following transcardial perfusion with heparin, 4% paraformaldehyde and 2 mM ProHance (Bracco Diagnostics), heads were decapitated and the skin, lower jaw, ears, and the cartilaginous nose tip were removed. The remaining skull containing the brain was soaked overnight in 4% paraformaldehyde/2 mM ProHance and then transferred to PBS, 0.02% sodium azide and 2 mM Prohance for at least 30 days prior to magnetic resonance imaging (MRI) acquisition [45]. …”

Section: Methodsmentioning

confidence: 99%

Neuroanatomy in mouse models of Rett syndrome is related to the severity of Mecp2 mutation and behavioral phenotypes

et al. 2017

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BackgroundRett syndrome (RTT) is a neurodevelopmental disorder that predominantly affects girls. The majority of RTT cases are caused by de novo mutations in methyl-CpG-binding protein 2 (MECP2), and several mouse models have been created to further understand the disorder. In the current literature, many studies have focused their analyses on the behavioral abnormalities and cellular and molecular impairments that arise from Mecp2 mutations. However, limited efforts have been placed on understanding how Mecp2 mutations disrupt the neuroanatomy and networks of the brain.MethodsIn this study, we examined the neuroanatomy of male and female mice from the Mecp2tm1Hzo, Mecp2tm1.1Bird/J, and Mecp2tm2Bird/J mouse lines using high-resolution magnetic resonance imaging (MRI) paired with deformation-based morphometry to determine the brain regions susceptible to Mecp2 disruptions.ResultsWe found that many cortical and subcortical regions were reduced in volume within the brains of mutant mice regardless of mutation type, highlighting regions that are susceptible to Mecp2 disruptions. We also found that the volume within these regions correlated with behavioral metrics. Conversely, regions of the cerebellum were differentially affected by the type of mutation, showing an increase in volume in the mutant Mecp2tm1Hzo brain relative to controls and a decrease in the Mecp2tm1.1Bird/J and Mecp2tm2Bird/J lines.ConclusionsOur findings demonstrate that the direction and magnitude of the neuroanatomical differences between control and mutant mice carrying Mecp2 mutations are driven by the severity of the mutation and the stage of behavioral impairments.

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Variations in post-perfusion immersion fixation and storage alter MRI measurements of mouse brain morphometry

Cited by 76 publications

References 31 publications

Kctd13 deletion reduces synaptic transmission via increased RhoA

Kctd13 deletion reduces synaptic transmission via increased RhoA

Distinct cerebellar foliation anomalies in a CHD7 haploinsufficient mouse model of CHARGE syndrome

Neuroanatomy in mouse models of Rett syndrome is related to the severity of Mecp2 mutation and behavioral phenotypes

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