Behavioral and molecular effects of Ubtf knockout and knockdown in mice

Hori, Roderick T.; Khan, Mohammad Moshahid; Xiao, Jianfeng; Hargrove, Phillip W.; Moss, Tom; LeDoux, Mark S.

doi:10.1016/j.brainres.2022.148053

Cited by 8 publications

(2 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These disruptions lead to pediatric neurodevelopmental regression starting at young onset (2.5 to 3 years). The degeneration starts with cognitive-motor deficits, reported in humans as well as knockout mice 7 . This regression is accompanied by dystonia, parkinsonism, severe intellectual disability, feeding difficulties, autistic-like behaviors, a slow loss of motor, cognitive and speech capabilities, as well as severe epilepsy [48][49][50][51][52] .…”

Section: Ubtfmentioning

confidence: 99%

“…On the genomic aspect, there has been more attention to of many variants in which chromosomal subregions are deleted or duplicated in an inherited and de novo manner as well 2 . Various genes and mutations have been reported to be associated with ASD, such as AVPR1a, CHD8, DISC1, 7Dup11.23, DYX1C1, GRIN2B, ITGB3, NLGN1, NLGN3, NRXN1, PARK2, PTB2, RELN, RPL10, SHANK3, SLC6A4, SLC1A4, UBTF, UB3A [2][3][4][5][6][7][8] . On the neurobiological aspect, no specific brain area nor system has been confirmed to be entirely associated with the disorder, but an overall brain impairment has been shown starting from childhood 3 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Early maturation and hyperexcitability is a shared phenotype of cortical neurons derived from different ASD-associated mutations

Hussein

Tripathi

Choudhary

et al. 2022

Preprint

View full text Add to dashboard Cite

Autism Spectrum Disorder (ASD) is mainly characterized by social and sensory-motor abnormal and repetitive behavior patterns. Over 1000 genetic variants were reported to be highly penetrant and causative of ASD. Many of these mutations cause comorbidities such as epilepsy and intellectual disabilities (ID). In this study, we measured cortical neurons derived from induced pluripotent stem cells (iPSCs) of patients with four mutations in the genes GRIN2B, SHANK3, UBTF, as well as chromosomal duplication in the 7q11.23 region. Using a whole-cell patch-clamp, we observed that the mutant cortical neurons demonstrated hyperexcitability and early maturation compared to control lines. These changes were characterized by higher sodium current, higher amplitude and rates of excitatory postsynaptic currents (EPSCs), and more evoked action potentials in response to current stimulation in early-stage cell development (3-5 weeks post differentiation). These changes that appeared in all the different mutant lines, together with previously reported data, indicate that an early maturation and hyperexcitability may be a convergent phenotype of ASD cortical neurons.

show abstract

Section: Ubtfmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Early maturation and hyperexcitability is a shared phenotype of cortical neurons derived from different ASD-associated mutations

Hussein

Tripathi

Choudhary

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

Transcription factor UBF depletion in mouse cells results in downregulation of both downstream and upstream elements of the rRNA transcription network

Theophanous,

Christodoulou,

Mattheou

et al. 2023

Journal of Biological Chemistry

View full text Add to dashboard Cite

Early maturation and hyperexcitability is a shared phenotype of cortical neurons derived from different ASD-associated mutations

et al. 2023

View full text Add to dashboard Cite

Autism Spectrum Disorder (ASD) is characterized mainly by social and sensory-motor abnormal and repetitive behavior patterns. Over hundreds of genes and thousands of genetic variants were reported to be highly penetrant and causative of ASD. Many of these mutations cause comorbidities such as epilepsy and intellectual disabilities (ID). In this study, we measured cortical neurons derived from induced pluripotent stem cells (iPSCs) of patients with four mutations in the genes GRIN2B, SHANK3, UBTF, as well as chromosomal duplication in the 7q11.23 region and compared them to neurons derived from a first-degree relative without the mutation. Using a whole-cell patch-clamp, we observed that the mutant cortical neurons demonstrated hyperexcitability and early maturation compared to control lines. These changes were characterized by increased sodium currents, increased amplitude and rate of excitatory postsynaptic currents (EPSCs), and more evoked action potentials in response to current stimulation in early-stage cell development (3–5 weeks post differentiation). These changes that appeared in all the different mutant lines, together with previously reported data, indicate that an early maturation and hyperexcitability may be a convergent phenotype of ASD cortical neurons.

show abstract

Behavioral and molecular effects of Ubtf knockout and knockdown in mice

Cited by 8 publications

References 32 publications

Early maturation and hyperexcitability is a shared phenotype of cortical neurons derived from different ASD-associated mutations

Early maturation and hyperexcitability is a shared phenotype of cortical neurons derived from different ASD-associated mutations

Transcription factor UBF depletion in mouse cells results in downregulation of both downstream and upstream elements of the rRNA transcription network

Early maturation and hyperexcitability is a shared phenotype of cortical neurons derived from different ASD-associated mutations

Contact Info

Product

Resources

About