These mice express mutant AChRε in muscle. They may be useful for studying slow-channel congenital myasthenic syndrome (SCCMS).
Christopher M. Gomez, The University of Chicago
Genetic Background | Generation |
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Allele Type |
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Transgenic (Inserted expressed sequence) |
These transgenic mice express the L269F mutant form of the adult murine cholinergic receptor, nicotinic, epsilon polypeptide (Chrne) under control of the murine creatine kinase, muscle (Ckm) promoter. Chrne encodes the acetylcholine receptor (AChr) epsilon subunit AChRε, a subunit of the adult skeletal muscle AChR. Expressed in the neuromuscular junction, AChRs are ligand-gated ion channels that open in response to acetylcholine to elicit endplate potentials that evoke the muscle fiber action potentials and muscular contraction. A point mutation was introduced in CHRNE resulting in the εL269F mutation present in the affected members of two families with the slow-channel congenital myasthenic syndrome (SCCMS). SCCMS is a dominantly inherited disorder of neuromuscular transmission, characterized by fatigability and progressive weakness and atrophy of skeletal muscles. Hemizygous and homozygous εL269F mice are viable and fertile with a fine tremor and slow progressive weakness and fatigability. They exhibit impaired neuromuscular transmission with prolonged duration of neuromuscular endplate currents, reduced quantal content, and reduced endplate current amplitudes. They also display degeneration of the postsynaptic membrane, damage to subsynaptic nuclei and mitochondria, calcium overload of the postsynaptic region, and activation of calpain and caspase proteases in the postsynaptic region.
A transgene was generated encoding the murine mutant cholinergic receptor, nicotinic, epsilon polypeptide (Chrne*L269F) under control of a murine creatine kinase, muscle (Ckm) promoter. A point mutation was introduced resulting in the εL269F mutation as present in the affected members of two families with the slow-channel congenital myasthenic syndrome (SCCMS). The 3' untranslated end of the εL269F cDNA was removed and replaced with the 3' UTR pf the neomycin resistance gene (neo) and an intron from the SV40 small t intron. This construct was microinjected into FVB/NJ fertilized oocytes, and mice from founder line 5, containing approximately 5 transgene copies, were bred to FVB/NJ mice for many generations to establish a colony. Upon arrival at The Jackson Laboratory, mice were bred to FVB/NJ inbred mice (Stock No. 001800) for at least one generation.
Expressed Gene | Chrne, cholinergic receptor, nicotinic, epsilon polypeptide, mouse, laboratory |
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Site of Expression |
Allele Name | transgene insertion 5, Christopher Gomez |
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Allele Type | Transgenic (Inserted expressed sequence) |
Allele Synonym(s) | epsilonL269F |
Gene Symbol and Name | Tg(Ckm-Chrne*L269F)5Cgz, transgene insertion 5, Christopher Gomez |
Gene Synonym(s) | |
Promoter | Ckm, creatine kinase, muscle, mouse, laboratory |
Expressed Gene | Chrne, cholinergic receptor, nicotinic, epsilon polypeptide, mouse, laboratory |
Strain of Origin | FVB/NJ |
Chromosome | UN |
Molecular Note | A transgene was generated encoding the murine mutant cholinergic receptor, nicotinic, epsilon polypeptide (Chrne*L269F) under control of a murine creatine kinase, muscle (Ckm) promoter. A point mutation was introduced resulting in the epsilonL269F mutation as present in the affected members of two families with the slow-channel congenital myasthenic syndrome (SCCMS). The 3' untranslated end of the epsilonL269F cDNA was removed and replaced with the 3' UTR pf the neomycin resistance gene (neo) and an intron from the SV40 small t intron. Line 5 was generated. |
When maintaining a live colony, hemizygous mice may be bred to wildtype (non-carrier) mice from the colony, or to FVB/NJ inbred mice (Stock No. 001800). Some mortality has been noted when breeding homozygous mice together.
When using the FVB-Tg(Ckm-Chrne*L269F)5Cgz/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #019931 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Heterozygous or wildtype for Tg(Ckm-Chrne*L269F)5Cgz |
Frozen Mouse Embryo | FVB-Tg(Ckm-Chrne*L269F)5Cgz/J | $2595.00 |
Frozen Mouse Embryo | FVB-Tg(Ckm-Chrne*L269F)5Cgz/J | $2595.00 |
Frozen Mouse Embryo | FVB-Tg(Ckm-Chrne*L269F)5Cgz/J | $3373.50 |
Frozen Mouse Embryo | FVB-Tg(Ckm-Chrne*L269F)5Cgz/J | $3373.50 |
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