B6SJL-Tg(Myh6-MYL3*A57G)#Dsc/Mmjax

Stock number: 040875
Product name: MYL3-A57G
Research areas: Cardiovascular Research, Internal/Organ Research, Research Tools

Description

MYL3-A57G transgenic mice harbor human MYL3 cDNA, which carries a A57G mutation, driven by the mouse Myh6 promoter. These mice may be useful when studying familial hypertrophic cardiomyopathy.

Of note, the donating laboratory has made a control MYL3-WT transgenic line available as RRID:MMRRC_075978-JAX.

Detailed description

The myosin, light polypeptide 3 (Myl3) gene encodes the myosin essential light chain 3 (ELC) protein, which is a component of the cardiac myosin complex and plays a critical role in cardiac muscle contraction. Mutations in this gene are associated with hypertrophic cardiomyopathy and other cardiac disorders. These MYL3-A57G transgenic mice harbor human MYL3 cDNA, which includes an amino acid substitution of alanine to glycine at position 57 (A57G), driven by the mouse myosin, heavy polypeptide 6, cardiac muscle, alpha (Myh6) promoter.

Hemizygous mice are viable and fertile. The donating laboratory has not evaluated homozygous mice. By 5-6 months of age, MYL3-A57G transgenic mice do demonstrate age-related cardiac hypertrophy, including increased left ventricular (LV) wall thickness, interstitial fibrosis, and diastolic dysfunction. These MYL3-A57G transgenic mice may be useful when studying familial hypertrophic cardiomyopathy.

Of note, the donating laboratory has made a control MYL3-WT transgenic line available as RRID:MMRRC_075978-JAX.

Development

The MYL3-A57G transgene was generated using human myosin, light polypeptide 3 (MYL3) cDNA, that contains an amino acid substitution of alanine to glycine at position 57 (A57G), driven by the mouse myosin, heavy polypeptide 6, cardiac muscle, alpha (Myh6) promoter. The final transgene construct included approximately 5.5kb of the mouse Myh6 promoter, including the first two exons and part of the third, followed by ~590bp of the human MYL3-A57G mutation and a 630bp 3' untranslated region (UTR) from the human growth hormone (hGH) transcript. The purified linearized DNA was microinjected into the pronuclei of fertilized mouse oocytes obtained from (C57BL/6XSJL)F1 matings. The donating laboratory has indicated that the transgene copy number and integration site are not known. The MYL3-A57G transgenic colony was maintained by crossing hemizygous mice to B6SJLF1/J mice. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish a live colony, an aliquot of frozen sperm was used to fertilize B6SJLF1/J oocytes.

Allele

Symbol: Tg(Myh6-MYL3*A57G)#Dsc
Name: transgene insertion, Danuta Szczesna-Cordary
MGI accession ID: MGI:5909257
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Synonyms: Tg-A57G
Marker symbol: Tg(Myh6-MYL3*A57G)#Dsc
Marker name: transgene insertion, Danuta Szczesna-Cordary
Marker synonyms: Tg-A57G
Chromosome: UN
Strain of origin: (C57BL/6 x SJL)F1
Molecular note: The human ventricular essential light chain (MYL2) cDNA with an alanine to glycine mutation at residue 57 (A57G) is under the control of the mouse alpha-myosin heavy chain promoter. Lines L1, L5, and L2 were generated, however the pound symbol (#) is used when line is not specified and/or lines are pooled.