FVB-Tg(Ckm-Chrne*L269F)5Cgz/J

Stock number: 019931
Research areas: Cell Biology Research, Neurobiology Research

Description

These mice express mutant AChRε in muscle. They may be useful for studying slow-channel congenital myasthenic syndrome (SCCMS).

Detailed description

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.

Development

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.

Allele

Symbol: Tg(Ckm-Chrne*L269F)5Cgz
Name: transgene insertion 5, Christopher Gomez
MGI accession ID: MGI:5468686
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(Ckm-Chrne*L269F)5Cgz
Marker name: transgene insertion 5, Christopher Gomez
Chromosome: UN
Strain of origin: FVB/NJ
Expressed genes: Chrne,cholinergic receptor, nicotinic, epsilon polypeptide,mouse, laboratory
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.