B6;DBA-Tg(Myl1-rtTA2S*M2)1Lach/J

Stock number: 032637
Product name: MDAFrtTA
Research areas: Research Tools

Description

MDAFrtTA mice are a Tet-On tool that allows conditional, doxycycline-inducible expression of the reverse tetracycline-controlled transactivator (rtTA) protein in skeletal muscle using the rat myosin light chain (Myl1) promoter.

Detailed description

MDAFrtTA mice are a Tet-On tool that allows conditional, doxycycline-inducible expression of the reverse tetracycline-controlled transactivator (rtTA) protein in skeletal muscle using the rat myosin light chain (Myl1) promoter. MYL1 is an ATPase cellular motor protein expressed in slow twitch muscles such as the soleus that is involved in the development of fast skeletal muscle. When mated to a second strain carrying a gene of interest under the regulatory control of a tetracycline-responsive promoter element (tetO), expression of the target gene may be regulated by the tetracycline analog, doxycycline (dox). In the presence of dox, transcription of the target gene is induced in cells where rtTA is expressed. Hemizygous MDAFrtTA transgenic mice are viable and fertile. The donating investigator reports that no homozygous mice are born from hemizygous breeding, indicating that homozygous mice may not be viable.

When bred to TREDT960I mice expressing a human DMPK genomic segment with 960 interrupted CTG repeats (CUG₉₆₀) under control of the tetO promoter (Stock No. 032050), the resulting double mutant mice when treated with doxycycline display clear, measurable reversible muscle wasting accompanied by severe histological defects including central myonuclei, reduced fiber cross sectional area, increased percentage of oxidative myofibers, and the presence of nuclear RNA foci that colocalize with Mbnl1 protein.

Development

MDAFrtTA mice express a modified reverse tetracycline-regulated transactivator (rtTA) with an increased doxycycline sensitivity and lower basal activity (rtTA2S-M2) driven by the rat myosin, light polypeptide 1 (Myl1) promoter. This transgene was microinjected into fertilized C57BL/6 x DBA oocytes, and founder mice were maintained on a mixed C57BL/6 x DBA background by the donating laboratory. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Allele

Symbol: Tg(Myl1-rtTA2S*M2)1Lach
Name: transgene insertion 1, Lewis A Chodosh
MGI accession ID: MGI:6117323
Generation method: Transgenic
Attributes: Transactivator
Synonyms: MDAFrtTA
Marker symbol: Tg(Myl1-rtTA2S*M2)1Lach
Marker name: transgene insertion 1, Lewis A Chodosh
Chromosome: UN
Strain of origin: C57BL/6 x DBA
Molecular note: The modified reverse tetracycline transactivator (rtTA) with an increased doxycycline sensitivity and lower basal activity (rtTA2S-M2) is expressed under the control of the rat myosin light chain 1 gene promoter and MLC1/3 enhancer. Expression is seen in skeletal muscle. Two lines were generated, with one studied further.