This Ryr1 knock-in strain carries the T4706M point mutation in exon 96 and may be useful in studies RYR1-associated myopathies.
Michael Goldberg, The RYR-1 Foundation
The targeted Ryr1 gene encodes a skeletal muscle ryanodine receptor that acts as a calcium channel between the sarcoplasmic reticulum and cytoplasm and is required for muscle fiber development. Mutations in this gene have been associated with RYR1-associated myopathies, malignant hyperthermia, central core disease, King-Denborough syndrome, minicore myopathy with external ophthalmoplegia, and congenital neuromuscular disease with uniform type 1 fiber. These mutant mice carry the T4706M point mutation in exon 96 of the Ryr1 gene. Homozygotes are viable and fertile. As the mice are characterized, we will modify the strain description and add phenotype data (June 2019).
A targeting vector containing a frt-flanked Neo cassette was used to introduce the Thr4706Met point mutation (ACG > ATG) in exon 96 of the Ryr1 gene and the selection cassette upstream of exon 96. The construct was electroporated into C57BL/6 derived iTL BF1 embryonic stem (ES) cells (C57BL/6 FLP) which express FLP recombinase vector to remove the selection cassette. Correctly targeted ES cells were injected into BALB/c blastocysts. The resulting chimeric animals were bred to C57BL/6 wildtype mice. Heterozygotes were intercrossed to generate homozygotes. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).
|Allele Name||targeted mutation 1.1, Michael Goldberg|
|Allele Type||Targeted (Humanized sequence)|
|Gene Symbol and Name||Ryr1, ryanodine receptor 1, skeletal muscle|
|Strain of Origin||C57BL/6|
|General Note||ES cell = iTL BF1 (C57Bl/6 FLP)|
|Molecular Note||The targeting vector contains as Thr4706Met point mutation (ACG to ATG) in exon 96 followed by an FRT-flanked neomycin cassette. Flp-mediated recombination removed the FRT-flanked neo cassette. THe T4706M mutation was identified in a patient with RYR1 related myopathy.|
When maintaining a live colony, these mice can be bred as homozygotes.
When using the Ryr1 T4706M Knock-in mouse strain in a publication, please cite the originating article(s) and include JAX stock #032636 in your Materials and Methods section.
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