B6SJL-Tg(Myh6-MYL2*D94A)1Dsc/Mmjax

Stock number: 040702
Product name: MYL2-D94A
Research areas: Cardiovascular Research, Internal/Organ Research, Research Tools

Description

MYL2-D94A transgenic mice harbor human MYL2 cDNA, which carries a D94A mutation, driven by the mouse Myh6 promoter. These mice may be useful when studying familial dilated cardiomyopathy.

Of note, the donating laboratory has made a control MYL2-WT transgenic line available as RRID:MMRRC_075975-JAX.

Detailed description

Ventricular myosin light chain 2, encoded by the Myl2 (myosin, light polypeptide 2, regulatory, cardiac, slow) gene, is essential in vertebrate smooth muscle contraction and has a regulatory role in striated slow twitch muscle contraction. Mutations in this gene have been associated with hypertrophic and dilated cardiomyopathies. These MYL2-D94A transgenic mice harbor human MYL2 cDNA, which includes an amino acid substitution of aspartic acid to alanine at position 94 (D94A), 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 months of age, MYL2-D94A male mice demonstrate left ventricular dilation as well as significant reduction in ventricular function (ejection fraction) compared to wildtype transgenic controls. Both male and female MYL2-D94A mice show symptoms of dilated cardiomyopathies by 12 months of age. These MYL2-D94A transgenic mice may be useful when studying familial dilated cardiomyopathy.

Of note, the donating laboratory has made a control MYL2-WT transgenic line available as RRID:MMRRC_075975-JAX.

Development

The MYL2-D94A transgene was generated using human myosin, light polypeptide 2, regulatory, cardiac, slow (MYL2) cDNA, that contains an amino acid substitution of aspartic acid to alanine at position 94 (D94A), 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 ~498bp of the human MYL2-D94A cDNA 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. Two founder lines were established, founder line L1 was further expanded. The donating laboratory has indicated that the transgene copy number and integration site are not known. The MYL2-D94A 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-MYL2*D94A)1Dsc
Name: transgene insertion 1, Danuta Szczesna-Cordary
MGI accession ID: MGI:6193897
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Synonyms: D94A-L1
Marker symbol: Tg(Myh6-MYL2*D94A)1Dsc
Marker name: transgene insertion 1, Danuta Szczesna-Cordary
Marker synonyms: D94A-L1
Chromosome: UN
Strain of origin: (C57BL/6 x SJL)F1
Molecular note: The human ventricular myosin regulatory light chain with an aspartic acid to alanine change at amino acid 94 (D94A) is under the control of the mouse alpha-myosin heavy chain promoter. Two lines, 1 and 2, were generated. Both lines show similar phenotypes and line 1 is entered as the representative line.