CHRNE Antibody
Description
Definition and Mechanism
The CHRNE antibody is a monoclonal or polyclonal antibody designed to bind specifically to the ε-subunit of the AChR. The ε-subunit replaces the fetal γ-subunit in adult muscle, forming the pentameric α₂βεδ receptor structure essential for neuromuscular transmission . Key features include:
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Epitopes: Targets regions such as amino acids (aa) 1–250 (Abcam, 4E10F6) , aa 21–239 (Antibodies-Online, ABIN5684150) , or aa 185–197 (rabbit polyclonal) .
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Applications: Western blot (WB), ELISA, flow cytometry (FACS), and immunohistochemistry (IHC) .
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Reactivity: Primarily human but cross-reacts with rat, mouse, and bovine in some formulations .
Detection in Neuromuscular Disorders
CHRNE antibodies are used to study AChR expression and dysfunction in CMS, particularly in low-expressor or slow-channel syndromes linked to CHRNE mutations . For example:
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Western Blot: Identifies ε-subunit defects in transfected cell lysates or recombinant proteins .
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ELISA: Quantifies ε-subunit levels in serum or tissue samples .
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Flow Cytometry: Assesses AChR clustering and surface expression in muscle cells .
Table 1: CHRNE Antibody Applications and Reactivity
Clinical Relevance in CMS
Mutations in CHRNE account for ~50% of CMS cases . Key findings include:
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Pathophysiology: Frame-shift mutations (e.g., c.632_633dupCG) reduce AChR surface expression, impairing signal transmission .
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Therapy: β2-adrenergic receptor agonists (e.g., salbutamol) stabilize neuromuscular junctions and reduce fatigue in CMS patients .
Table 2: CHRNE Mutations and Clinical Outcomes
| Mutation Type | Mechanism | Treatment Response | Source |
|---|---|---|---|
| Homozygous frameshift | Nonsense-mediated decay | Salbutamol + Cholinesterase inhibitors | |
| Heterozygous missense | Impaired channel gating | β2-agonists |
Key Antibodies
| Catalog No. | Host | Epitope (aa) | Applications | Reactivity | Price Range |
|---|---|---|---|---|---|
| 4E10F6 | Mouse | 1–250 | WB, ELISA | Human, Rat | $314–$565 |
| ABIN5684150 | Mouse | 21–239 | WB, ELISA, FACS | Human | $250 |
| PA5-97589 | Rabbit | Full-length | WB, IHC | Human | N/A |
Challenges and Future Directions
Product Specs
Target Background
Upon acetylcholine binding, the acetylcholine receptor (AChR) undergoes a significant conformational change affecting all subunits. This leads to the opening of an ion channel spanning the plasma membrane.
The following studies highlight the role of CHRNE gene mutations and their impact on acetylcholine receptor function:
- A study reported a 31.9% pretest probability of a CHRNE c.130dupG mutation in at least one allele of Congenital Myasthenic Syndrome (CMS) patients. This percentage remained substantial (26.4%) even when considering only homozygous patients, increasing further when limited to patients with impaired eye movement and pyridostigmine-responsive symptoms. PMID: 29383513
- Specific COLQ, RAPSN, and CHRNE mutations exhibit ethnic population-specific prevalence in Israel, necessitating consideration during CMS diagnosis. PMID: 28024842
- Mutational analysis identified a homozygous 1293insG mutation in CHRNE, a known low-expressor receptor mutation associated with epidermolysis bullosa simplex and CMS. PMID: 21175599
- A new mouse model for slow-channel CMS was developed, induced by the AChR epsilonL221F mutation. PMID: 22178625
- Three siblings presented with clinical features consistent with homozygous CHRNE mutations, illustrating the variable clinical presentation of congenital myasthenia subtypes and the importance of accurate genotyping for treatment selection. PMID: 21150643
- Targeting nAChR offers a potential strategy for mitigating neurodegeneration resulting from hyperphosphorylation of tau protein. PMID: 21715663
- Mutations in the epsilon subunit altered AChR channel Ca2+ permeability; varepsilon(L269F) increased permeability, while varepsilon(I257F) decreased it. PMID: 21470676
- Research analyzed symmetry at the extracellular domain-transmembrane domain interface in acetylcholine receptor channel gating. PMID: 20864527
- Studies revealed a roughly 10-fold difference in ACh binding affinity between the two sites on the closed receptor in the wild type. In the epsilonL221F mutation, the lower affinity site showed increased affinity, resulting in greater similarity between the two sites. PMID: 12562900
- A deletion in exon 7 of CHRNE was identified. The entire CHRNE gene (12 exons, 11 introns) was cloned and expressed in COS cells. PMID: 14532324
- Mutations within muscle AChRs are the most common cause of CMS, primarily located in the epsilon-subunit gene, leading to AChR deficiency. PMID: 14592868
- AChR epsilon-chain peptides demonstrated in vitro activation of peripheral blood mononuclear leukocytes from myasthenia gravis (MG) patients, but not in non-myasthenic subjects. PMID: 15652413
- A patient with CMS was reported, exhibiting two compound heterozygous mutations in the CHRNE gene. PMID: 16087917
- A patient with slow-channel CMS carrying a novel valine to phenylalanine mutation in the epsilon subunit of the AChR was identified. PMID: 16198106
- The intrinsically high Ca2+ permeability of human AChRs likely contributes to endplate myopathy development when AChR channel opening events are prolonged due to altered channel kinetics. PMID: 16527851
- Increased Ca2+ permeability of mutant receptors overrides the protective effect of desensitization and, along with prolonged AChR channel opening, contributes to slow channel syndromes. PMID: 17272341
- Upon AChR activation, GABP recruits the histone acetyltransferase (HAT) p300 to the AChR epsilon subunit promoter, while recruiting histone deacetylase HDAC1 when the promoter is inactive. PMID: 17304221
- A synonymous mutation in CHRNE was identified that creates a cryptic splice site; mRNA quantification suggests this mutation is disease-causing. PMID: 17363247
- Higher mRNA abundance for the AChR epsilon-subunit compared to other subunits suggests a unique role in autosensitization in MG-associated thymomas (types A or AB). PMID: 18657869
- Findings strongly suggest that epsilon1293insG mutations in a myasthenic syndrome originated from an ancient single founder event in the North African population. PMID: 19064877
- Mutations in the acetylcholine receptor (AChR) epsilon-subunit gene underlying congenital myasthenic syndromes were identified in nine Dutch patients (seven kinships). PMID: 19544078
