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Validated All-in-One™ qPCR Primer for HTT(NM_002111.6) Search again
Product ID:
HQP008744
(click here to view gene annotation page)
Powered by BiozSpecies:
Human
Symbol:
Alias:
HD, IT15, LOMARS
Gene Description:
huntingtin
Target Gene Accession:
NM_002111.6(click here to view gene page)
Estimated Delivery:
Approximately 1-3 weeks, but may vary. Please email sales@genecopoeia.com or call 301-762-0888 to confirm ETA.
Important Note:
By default, qPCR primer pairs are designed to measure the expression level of the splice variant (accession number) you selected for this gene WITHOUT consideration of other possible variants of this gene. If this gene has multiple variants, and you would like to measure the expression levels of one particular variant, multiple variants, or all variants, please contact us for a custom service project at inquiry@genecopoeia.com.
Validated result:
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| A | B |
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Each All-in-One™ qPCR Primer is experimentally validated to yield a single dissociation curve peak and to generate a single amplification of the correct size for the targeted gene. A cDNA Pool, containing reverse transcript products of 8 different human tissue total RNA(Liver, Testis,Muscle,Thyroid,Brain,Spleen,Stomach,Small Intestine)),was used as the qPCR validation template. qPCR was performed using 0.2 µM primer with 2XAll-in-One™ qPCR Mix (Catalog#: QP001,QP002,QP004,QP005). Reactions were incubated for 10min. at 95°C, followed by 40 cycles of 95°C for 10 sec.; 60°C, 20 sec. and 72°C, 15sec. using Bio-Rad iQ5™ Instrument. At the end of the last cycle, temperature was increased from 72 to 95°C to produce a melting curve. Panel A: Validated Result for Amplification Curve; Panel B: Validated Result for Melting Curve. |
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Summary
Huntingtin is a disease gene linked to Huntington's disease, a neurodegenerative disorder characterized by loss of striatal neurons. This is thought to be caused by an expanded, unstable trinucleotide repeat in the huntingtin gene, which translates as a polyglutamine repeat in the protein product. A fairly broad range in the number of trinucleotide repeats has been identified in normal controls, and repeat numbers in excess of 40 have been described as pathological. The huntingtin locus is large, spanning 180 kb and consisting of 67 exons. The huntingtin gene is widely expressed and is required for normal development. It is expressed as 2 alternatively polyadenylated forms displaying different relative abundance in various fetal and adult tissues.
Gene References into function
- wild type huntingtin reduces the cellular toxicity of mutant huntingtin in mammalian cell models of Huntington's disease
- Normal huntingtin has an important role in neuronal cell survival, and loss of function of the normal protein may contribute to HD as well as gain of function of the abnormal huntingtin.
- In human fibroblasts from normal and HD patients, huntingtin localized diffusely in the nucleus and in subnuclear compartments identified as speckles, promyelocytic leukemia protein bodies, and nucleoli
- Effects of intracellular expression of anti-huntingtin antibodies of various specificities on mutant huntingtin aggregation and toxicity.
- arfaptin 2 is involved in regulating huntingtin protein aggregation
- Huntingtin is found in the perinuclear region along with microtubules, and in the centrosomal region along with gamma-tubulin. Inclusions are found in perinuclear locations because the beta-tubulin binding property of huntingtin brings it there.
- These results suggest that medium-sized spiny striatal neurons are more vulnerable to NR2B-subtype NMDAR-mediated cell death in a transgenic mouse model of HD expressing full-length mutant huntingtin, compared with wild-type mice.
- findings suggest that altered gene expression may result from the interactions of soluble mutant huntingtin with nuclear transcription factors, rather than from the depletion of transcription factors by nuclear inclusions
- huntingtin interacts with Sp1 and TAFII130; transcriptional activity of SP1 and TAFII130 disrupted in early Huntingtin's Disease
- mutant huntingtin containing an expanded polyglutamine stretch induces neuronal death.
- Impaired glutamate transport and glutamate-glutamine cycling: downstream effects of the Huntington mutation in transgenic mice
- Proteases acting on mutant huntingtin generate cleaved products that differentially build up cytoplasmic and nuclear inclusions.
- An upstream open reading frame impedes translation of the huntingtin gene
- Role of huntingtin in human health and disease [review]
- Context-dependent neurodegeneration in huntington disease may be mediated by different N-terminal huntingtin fragments
- In cases where the mother is known to be not a carrier, early Huntington disease prenatal diagnosis is possible by semiquantitative fluorescent-PCR of trace fetal dna in maternal blood samples
- may function as a transcriptional coactivator of nuclear hormone receptors.
- HD mutation is accompanied by a dramatic decline in Ca2+-triggered exocytosis of neurotransmitter and the decline in neurotransmitter release is a direct consequence of complexin II depletion.
- polyglutamine-expanded huntingtin induces tyrosine phosphorylation of N-methyl-D-aspartate receptors
- Huntingtin and huntingtin-associated protein 1 influence neuronal calcium signaling mediated by inositol-(1,4,5) triphosphate receptor type 1.
- Regulated expression of huntingtin (Huntington disease) induced reversible striatal neuropathology typical for Huntington disease.
- theories differ with respect to subcellular distribution of HD at initiation of toxicity in Huntington's diease: nuclear if cleaved and cytoplasmic in the absence of cleavage
- Here we show dramatic mutation length increases (gains of up to 1000 CAG repeats) in human striatal cells early in the disease course, most likely before the onset of pathological cell loss.
- huntingtin has a role in regulating cysteine string protein inhibition of N-type calcium channels
- modeling framework based on a key analogy of the physicochemical properties of the huntingtin exon1 fragment to block copolymers
- genome-wide screens were performed in yeast to identify genes that enhance the toxicity of mutant huntingtin;the genes clustered in the functionally related cellular processes of response to stress, protein folding & ubiquitin-dependent protein catabolis
- A patient with triosephosphate isomerase (TPI) deficiency exhibited worsening of abnormal involuntary movements of the dystonic type and developed psychiatric symptoms while on selegiline.
- Nonnuclear events induced by cytoplasmic huntingtin aggregation play a central role in the progressive neurodegeneration observed in Huntington's disease.
- Inhibiting the interaction of calmodulin with transglutaminase and huntingtin protein could decrease cross-linking and diminish huntingtin aggregate formation in the HD brain
- Rapid clearance through the ubiquitin-proteasome pathway slows huntingtin aggregate formation, yet increases cellular toxicity. Polyglutamine neurotoxicity may be triggered by non-aggregated protein and aggregate formation may be a defense mechanism
- Our findings using htt exon 1 suggest that the process of mutant htt aggregation rather than the resulting inclusion body is critical for neuronal cell death
- the mutant huntingtin protein significantly decreased the Ca2+ threshold necessary to trigger MPT pore opening which accompanied by a significant release of cytochrome c
- Causes huntingti0n disase when transfected into mice.
- In Huntington's disease, expansion occurs in the huntingtin protein. (review)
- Time course of striatal degeneration produced by expanded huntingtin (Exp-Htt)occurs rapidly: at 48 h post-transfection, 60% of cultured striatal neurons expressing Exp-Htt have apoptotic characteristics including fragmented DNA and neuritic retraction.
- unusual infantile onset of the disease in a little girl who presented with a history of seizures and psychomotor regression starting at the age of 3 years
- is involved in fast axonal trafficking
- siRNA is not directly linked to DNA methylation at the target huntingtin genomic locus in human cells
- Growing evidence discussed in this review suggests that mutant huntingtin mediates multiple pathological pathways causing selective neurodegeneration in brains of Huntington's disease patients.
- Here we report the purification of huntingtin aggregates from postmortem Huntington's disease brains.
- Transcription from three initiation sites located within a 50-bp region in the phosphodiesterase 10A-specific promoter is differentially affected by the presence of the mutant huntingtin transgene.
- These results suggest that Tpr has a role in the nuclear export of N-terminal htt and that polyQ expansion reduces this nuclear export to cause the nuclear accumulation of htt.
- Data show that polyglutamine-expanded mutant huntingtin suppresses expression of the A2A adenosine receptor by inhibiting its core promoter at least partially by preventing CREB binding.
- Repeats of 40 or larger are associated with disease expression, whereas repeats of 26 and smaller are normal. Intermediate numbers of repeats, between 27 and 35, are not associated with disease expression but may expand in paternal transmission
- arfaptin 2 phosphorylation at Ser260 by Akt inhibits PolyQ-huntingtin-induced toxicity by rescuing proteasome impairment
- presence and pattern of huntingtin protein (htt) phosphorylation in the brain indicates that this dynamic post-translational modification is important for the regulation of htt and may contribute to selective neurodegeneration seen in Huntington disease
- Our findings suggest that caspase cleavage of Htt is cytoplasmic and precedes sorting to specific perinuclear sites followed by nuclear translocation in HD patient tissue.
- These data predict that the ability of cdk5 phosphorylation to protect against htt cleavage, aggregation, and toxicity is compromised in cells expressing toxic fragments of htt.
- Adenovirus-mediated silencing of huntingtin expression was effected by shRNA.
- Reduced hippocampal neurogenesis may be a novel neuropathological feature in huntingtin transgenic mice that could be assessed when evaluating potential therapies.
- mutant huntingtin specifically affects CBP and not p300 both at the early and later time points, via multiple mechanisms
- The present study demonstrates that viral vectors coding for mutant huntingtin provides an advantageous system for histological and biochemical analysis of HD pathogenesis in primary striatal cultures.
- Huntingtin directly binds membranes through electrostatic interactions with acidic phospholipids
- There is an interplay between huntingtin, ataxin-2 and endophilin proteins in plastin-associated cellular pathways.
- The polyglutamine tract in huntingtin appears to regulate mitochondrial ADP-phosphorylation in a Ca2+-dependent process that fulfills the genetic criteria for the Huntington's disease trigger of pathogenesis.
- Our data indicate that htt(exon1) enhances calcium influx by blocking syntaxin 1A inhibition of N-type calcium channels and attributes a key role for htt N-terminal fragments in the fine tuning of neurotransmission.
- nuclear exon 1 mutant protein is sufficient to induce cytoplasmic neurodegeneration and transcriptional dysregulation; cytoplasmic mutant exon 1 htt, if present, contributes to disease progression
- HDAC6-dependent retrograde transport on microtubules is used by cells to increase the efficiency and selectivity of autophagic degradation of aggregated huntingtin
- Yeast hsp104 overexpressed in transgenic mice that express the first 171 residues of mutant human huntingtin reduces polyglutamine aggregation and increases survival of Huntington's disease (HD) model mice by 20%.
- p53 protein can regulate huntingtin expression at transcriptional level
- p62 may, via LC3, be involved in linking polyubiquitinated protein aggregates to the autophagy machinery and has a protective effect on huntingtin-induced cell death
- Mutant htt in cultured astrocytes decreased their protection of neurons against glutamate excitotoxicity. These findings suggest that decreased glutamate uptake caused by glial mutant htt may critically contribute to neuronal excitotoxicity in HD
- NAKAP-HypA scaffold is a potential nuclear docking site for huntingtin protein and may contribute to the nuclear accumulation of huntingtin observed in HD.
- Transgenic mice over-expressing full-length wild-type huntingtin were dramatically protected from apoptosis and caspase-3 activation.
- The present results strongly suggest that complex II defects produced by N-terminus fragment of mutated huntingtin in HD may be instrumental in striatal cell death.
- We conclude that in cortical neurons, an early event in HD pathophysiology is the aberrant mobility and trafficking of mitochondria caused by cytosolic Htt aggregates.
- age-dependent decrease of beclin 1 expression may lead to a reduction of autophagic activity during aging, which in turn promotes the accumulation of mutant Htt and the progression of the disease
- report the expression and preliminary characterization of recombinant full-length wild-type human htt. Our results support a model of htt composed entirely of HEAT repeats that stack to form an elongated superhelix
- Mutated huntingtin (htt) is ubiquitously expressed in tissues of Huntington's disease (HD) patients. Another notable feature was the formation of htt inclusions in differentiated myoblasts.
- These results are consistent with proteolysis of htt at the caspase-6 cleavage site being an important event in mediating neuronal dysfunction and neurodegeneration in HD.
- More than six novel serine phosphorylation sites have been identified within Htt, one of which lies in the proteolytic susceptibility domain.
- htt and GASP2 form a complex in cotransfected mammalian cells
- Study uses an inducible yeast model of HD by expressing a mutant human huntingtin fragment and showed that in yeast cells expressing the mutant fragment cell respiration was progressively reduced after 4-6 h of induction with galactose.
- The effect of mutations in huntingtin on calcium metabolism in the mitochondria of corpus striatum neuron cell lines is reported.
- context dependent transcriptional dysregulation may contribute to differential toxicity of various N-terminal htt fragments
- Autopsy-proven Huntington's disease with 29 trinucleotide repeats.
- These data demonstrate that huntingtin inhibits caspase-3 activity.
- These data demonstrate that mutant huntingtin expression has potent cardiotoxic effects; cardiac failure may be a significant complication of this important experimental model of HD.
- The sub-cellular localization is most strongly influenced by the first 17 amino acids, with this sequence critically controlling Httex1p mitochondrial localization and also promoting association with the endoplasmic reticulum (ER) and Golgi.
- Hrd1 is a novel htt-interacting protein that can target pathogenic httN for degradation and is able to protect cells against httN-induced cell death.
- A new role is revealed for huntingtin in the regulation of the post-Golgi trafficking of proteins that follow the regulated secretory pathway.
- analysis of the specific interactions between Htt proline-rich region (PRR) and its binding partners as well as the alteration of these interactions that involve PRR
- A role for huntingtin in the intracellular trafficking of proteins required for the construction of the extracellular matrix.
- Here, we report that upon the formation of huntingtin aggregates; endogenous cytosolic huntingtin, Hsc70/Hsp70 (heat shock protein and cognate protein of 70kDa) and syntaxin 1A become aggregate-centered.
- Review discusses the role of normal huntingtin in transcriptional regulation and misregulation in Huntington's disease in relation to potentially analogous model systems, and to other polyglutamine disease proteins [review]
- Expression of single, isolated ubiquitin-interacting motifs inhibit aggregation of mutant huntingtin and could serve as potential inhibitors of polyQ-aggregation in vivo.
- The tgHD rat model reflects to a remarkable extent the cellular and subcellular neuropathological key features as observed in human HD and HD mouse brains and hints of changes in limbic forebrain systems.
- mutant htt alters the activation of type 2 transglutaminase in response to certain stimuli
- the CAG repeat is unstable in all cell types tested although neurons tend to have longer mutation length gains than glia
- Testicular pathology results from a direct toxic effect of mutant huntingtin in the testis and is supported by the fact that huntingtin is highly expressed in the affected cell populations in the testis.
- Seven interacting proteins from among 11 tested were able to co-immunoprecipitate with full-length Htt from mouse brain.
- Mutant huntingtin protein effects disease-related transcription in the brain.
- HD facilitates dynein-mediated vesicle transport.
- Wild-type huntingtin is a component of the DNA damage response signal in neurons.
- Repeat-length changes were dependent upon the sex of the transmitting parent, sex of the offspring, and parental CAG repeat length but not parental age or birth order. Genetic factors play a role in intergenerational CAG repeat instability.
- The results definitely confirm the diagnosis of HD and indicate the CAG trinucleotide repeat expansion of IT15 gene in this HD family.
- Rather than a direct impact on the mitochondrion, the polyglutamine tract may modulate some aspect of huntingtin's activity in extra-mitochondrial energy metabolism.
- Mutated Htt-exon 1 could mimic the cellular phenotypes observed in Huntington's disease.
- The present study, has confirmed, by confocal microscopy and immunoprecipitation, that HYPK interacts with the N-terminal of Htt.
- While cortical and striatal neurons can survive nearly a year with nuclear and extranuclear aggregates of mutant huntingtin, such lengthy survival does reveal cortical and striatal abnormality brought on by the truncated mutant protein.
- CAG repeats instability and mutant Htt are causative factor in mtDNA damage in Huntington disease
- A review of possible mechanisms to explain how mutant huntingtin can paradoxically protect neurons from death in transgenic mice.
- These results suggest that the polyQ domain, but not the polyP domain, plays a role in the sequestration of GAPDH to aggregates by mutant htt
- These results suggested that the HspB8-Bag3 complex might stimulate the degradation of Htt43Q by macroautophagy.
- expanded-huntingtin-induced transcriptional dysregulation and striatal death associated with with Mitogen- and stress-activated protein kinase-1 deficiency.
- Striatal neurons responded to the expression of a mutant huntingtin protein by activating protective mechanisms that modify NMDA receptor-mediated excitotoxic damage in transgenic mice.
- huntingtin toxicity in cell models and neurons is enhanced by Pak1 overexpression
- A linkage disequilibrium was found between Japanese HD chromosomes and (CCG)10, whereas western HD chromosomes are strongly associated with (CCG)7.
- Analysis of the aggregation-prone protein Htt encoded by HD gene exon 1 containing polyglutamine expansions (Htt86Q) revealed that 17 residues in the NH(2)-terminal of this protein are indispensable for its aggregate formation.
- Huntington gene mutation is associated with Huntington disease
- huntingtin fragment proteins with expanded polyglutamine repeats causes cell death in neuronal PC6.3 cell that involves endoplasmic reticulum stress.
- In primary striatal cultures, dopamine increases the toxicity of an N-terminal fragment of mutated huntingtin (Htt-171-82Q).
- Mutant huntingtin reduces the distribution and transport rate of mitochondria in transgenic neuronal cells.
- Both wheel running and environmental enrichment rescued HD-induced abnormal habituation of locomotor activity and exploratory behavior in the open field.
- Alteration of histone monoubiquitylation by mutant huntingtin is key pathogenic mechanism in Huntington's disease(HD). These findings aprovide rationale for targeting histone monoubiquitylation for therapy in HD.
- The nucleus is the primary site of htt cleavage at amino acid 586 by caspase 6.
- the intrabody reduces the specific neurotoxicity of cytoplasmic mutant huntingtin and its associated neurological symptoms by preventing the accumulation of mutant huntingtin in neuronal processes and promoting its clearance in the cytoplasm
- Studies using transgenic mice and monkeys suggest that the neuropathology of Huntington's disease is due to the accumulation of N-terminal mutant htt fragments of mutant htt.
- A common motif targets huntingtin and the androgen receptor to the proteasome
- demonstration of in vivo cell-autonomous transcriptional dysregulation in an HD transgenic mouse model
- the widely used mutant huntingtin-exon 1 CAG repeat HD transgenic mice model (R6/2) (with 144 CAG repeat and exon 1) during late-stage pathology, had increases in proteasome activity in the striatum
- 244 Patients with the diagnosis of Huntington's Disease and without mutation of the IT15 gene revealed one case of SCA17 but did not disclose the presence of two other diseases with a similar clinical manifestation: DRPLA and HDL2.
- Data indicate that Drosophila and Human Htt share biological properties, and confirm a model whereby Engrailed activates endogenous dhtt, which in turn prevents polyQ-hHtt-induced phenotypes
- REST/NRSF, dynactin p150(Glued), huntingtin, HAP1, and RILP form a complex involved in the translocation of REST/NRSF into the nucleus and HAP1 controls REST/NRSF cellular localization in neurons
- Results suggest that weight loss in Huntington disease is directly linked to CAG repeat length and is likely to result from a hypermetabolic state.
- In all Huntington disease cases studied, TDP-43 was frequently colocalized with huntingtin in dystrophic neurites and various intracellular inclusions, but not in intranuclear inclusions.
- findings indicate that mutant huntingtin with an extremely long polyQ tract is hindered in its nuclear entry and is expressed at diminished levels, with pathogenicity resultingly diminished
- Cells expressing Htt proteins with 74 or 138 polyglutamine repeats were more sensitized to oxidative stress-induced mitochondria fragmentation and had reduced ATP levels.
- study examined the effect of varying the CAG repeat length (from 170 to 450) and found that increasing the repeat length delayed onset of disease and prolonged survival in transgenic mice