Defects in UPF3B are the cause of a syndromic form of mental retardation, mental retardation syndromic X-linked type 14 (MRXS14) [MIM:300676]. A subset of individuals with MRXS14 are also either diagnosed with autism or are found to exhibit autistic features (Tarpey et al., 2007; Laumonnier et al., 2010; Addington et al., 2011; Lynch et al., 2012).
Molecular Function
This gene encodes a protein that is part of a post-splicing multiprotein complex involved in both mRNA nuclear export and mRNA surveillance. The encoded protein is one of two functional homologs to yeast Upf3p. mRNA surveillance detects exported mRNAs with truncated open reading frames and initiates nonsense-mediated mRNA decay (NMD). When translation ends upstream from the last exon-exon junction, this triggers NMD to degrade mRNAs containing premature stop codons. This protein binds to the mRNA and remains bound after nuclear export, acting as a nucleocytoplasmic shuttling protein. It forms with Y14 a complex that binds specifically 20 nt upstream of exon-exon junctions.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Mutations in UPF3B, a member of the nonsense-mediated mRNA decay complex, cause syndromic and nonsyndromic mental retardation.
Upf3b-null homozygous mice exhibit deficits in prepulse inhibition (PPI) and fear-conditioned learning. Upf3b-null mice also display defects in dendritic spine maturation of cortical pyramidal neurons.
References
Type
Title
Author, Year
Primary
A Upf3b-mutant mouse model with behavioral and neurogenesis defects.
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
ESC clone harboring gene trap cassette insertion in intron 1 was used to inject into donor blastocysts to generate chimeric Upf3b-mutant mice. Global Upf3b-mutant mice were obtained following breeding for germline transmission.
Allele Type: Knockout
Strain of Origin: C57BL/6
Genetic Background: C57BL/6
ES Cell Line: Mutant ES Cell Line: C57BL/6
Model Source:
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
ESC clone harboring gene trap cassette insertion in intron 1 was used to inject into donor blastocysts to generate chimeric Upf3b-mutant mice. Global Upf3b-mutant mice were obtained following breeding for germline transmission.
Allele Type: Knockout
Strain of Origin: C57BL/6
Genetic Background: C57BL/6
ES Cell Line: Mutant ES Cell Line: C57BL/6
Model Source:
Description: Upf3b-mutant mice show abnormal sleep behaviors compared to controls. specifically, upf3b-mutant mice differ from the control mice in time spent in wakefulness, slow wave sleep, and rem sleep. moreover, upf3b-mutant mice had more episodes of vigilance states that the average episode durations were shorter compared to conrols.
Exp Paradigm: NA
Description: Upf3b-mutant mice show abnormal paw-clasping behavior compared to controls. specifically, significantly more upf3b-mutant mice engage in no paw-clasping behavior, significantly fewer upf3b-mutant mice engage in occasional front paw-clasping behavior, and significantly more upf3b-mutant mice engage in frequent front paw-clasping behavior compared to controls.
Exp Paradigm: NA
Description: Upf3b-mutant mice show reduction in the number of mature dendritic spines but no difference in the number of immature spines compared to controls.
Exp Paradigm: NA
Description: Upf3b-mutant mice show reduction in dendritic spine density in cortical pyramidal neurons and dentate granule cells of the hippicampus but not the hippocampal ca1 pyramidal neurons compared to controls.
Exp Paradigm: NA
Description: Upf3b-mutant mice show deficiency in the magnitude of the acoustic startle response compared to controls. specifically, their deficiency is specific to low intensity 90-100 db range pulses, whereas they respond normally to 115-120 db range pulses.
Exp Paradigm: NA
Description: Upf3b-mutant mice show profound defect in prepulse inhibition compared to controls. specifically, upf3b-mutant mice show lower prepulse inhbition across different pulse intensities (78 db, 82 db, and 86 db) as well as across different 25-500 ms prepulse intervals compared to controls.
Exp Paradigm: NA
Description: Upf3b-mutant mice show no detectable levels of upf3b protein in the whole brain, hippocampus, or cerebral cortex compared to controls.
Exp Paradigm: Western blot
Description: Upf3b-mutant mice show no detectable levels of upf3b protein in the whole brain, hippocampus, or cerebral cortex compared to controls.
Exp Paradigm: Immunofluorescence staining
Description: Upf3b-mutant mice show a total of 129 misregulated genes, 109 of which are upregulated and 20 downregulated compared to controls.
Exp Paradigm: NA
Description: Upf3b-mutant mice show profound defect in prepulse inhibition compared to controls. specifically, upf3b-mutant mice show lower prepulse inhbition across different pulse intensities (78 db, 82 db, and 86 db) as well as across different 25-500 ms prepulse intervals compared to controls.
Exp Paradigm: NA
