C57BL/6-Tg(ACTA1-FRG1)highRotu/J

Stock number: 036978
Product name: HSA-FRG1-high
Research areas: Neurobiology Research

Description

HSA-FRG1-high mice may be useful when studying Facioscapulohumeral muscular dystrophy.

Detailed description

HSA-FRG1-high mice express the human FRG1 (FSHD region gene 1) under control of the human skeletal α-actin (ACTA1) gene promoter. FSHD (Facioscapulohumeral muscular dystrophy) is an autosomal dominant neuromuscular disorder in which patients carry deletions of an integral number of tandem 3.3-kilobase repeat units, termed D4Z4, located on chromosome 4q35. D4Z4 contains a transcriptional silencer whose deletion leads to overexpression in FSHD skeletal muscle of 4q35 genes located upstream of D4Z4 including FRG1, FRG2 or ANT1. FRG1 is a nuclear protein involved in pre-messenger RNA splicing. FSHD initially affects the skeletal muscles of the face, scapula, and upper arms with progressive weakness in other areas of the body.

HSA-FRG1-high mice carry 9 copies of the transgene and express over 40x the amount of FRG1 expressed by wildtype (WT) mice. These mice develop a muscular dystrophy with features characteristic of the human disease such as abnormal spinal curvature, progressive muscle dystrophy, and skeletal muscle atrophy. They weigh 60% of the body weight of WT mice due to muscle atrophy and reduced tolerance to exercise similar to a mouse model for Duchenne muscular dystrophy (DMD) (Dmd^mdx see Stock No. 001801). Hemizygous HSA-FRG1-high mice are viable and fertile.

Development

The HSA-FRG1-high transgene was designed with the human FRG1 (FSHD region gene 1) under control of the human skeletal α-actin (ACTA1) gene promoter. The transgene was microinjected into fertilized C57BL/6 oocytes, and mice from founder line Tg42, carrying 9 copies of the transgene, were maintained on a C57BL/6J background. Upon arrival at The Jackson Laboratory, transgenic mice were bred to C57BL/6J inbred mice (Stock No. 000664) to establish the colony.

Allele

Symbol: Tg(ACTA1-FRG1)highRotu
Name: transgene insertion high, Rossella Tupler
MGI accession ID: MGI:3817488
Generation method: Transgenic
Attributes: Inserted expressed sequence
Synonyms: FRG1-high; H-FRG1^Tg
Marker symbol: Tg(ACTA1-FRG1)highRotu
Marker name: transgene insertion high, Rossella Tupler
Marker synonyms: FRG1-high
Chromosome: UN
Strain of origin: C57BL/6
Molecular note: The human promoter was used to drive ubiquitous expression. At least 3 lines were created (named for expression levels of the transgene; low, medium and high).