D2.129(B6)-Utrn^tm1Ked/J

Stock number: 016904
Product name: D2 utrn -
Research areas: Neurobiology Research, Research Tools

Description

This Utrn targeted mutation mouse strain may be useful in studies of neuromuscular junctions, and hereditary neuropathies, specifically Duchenne Type Muscular Dystrophy.

Detailed description

Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (protein) is detected by Western blot analysis of kidney, lung and brain tissues. Levels of transcript are significantly reduced, as detected by RNase protection assay. Neuromuscular junctions from homozygotes lack extrasynaptic nerve sprouts, exhibit reduced postsynaptic membrane folding and fewer (approximately 40% reduction) acetylcholine receptors. The amplitude of miniature endplate currents (in extensor digitorum longus muscle) is reduced by 20%. Homozygotes exhibit abnormal Schwann cell compartments and reduced internodal length.

When bred with mice carrying the Dmd^mdx allele (see Stock No. 001801) the resulting double mutant mice exhibit a more severe phenotype than single Dmd^mdx mutants: earlier onset of muscle dystrophy (degeneration, macrophage infiltration and necrosis), weight loss after weaning, joint contractures, kyphosis, dystrophy of extraocular muscles, abnormal electrocardiograms, infertility and premature death. This double mutant strain is a model for Duchenne Type Muscular Dystrophy.

When bred with mice carrying the Dmd^mdx-3Cv allele (see Stock No. 002377), the resulting double mutant mice develop skeletal muscle abnormalities similar to the Dmd^mdx, Utrn^tm1Ked double mutant, but lack pathology of nonmuscle tissues.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

A targeting vector containing a PGK-Neo cassette was used to disrupt exon 7. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl⁺ derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting male chimeric animals were crossed to (DBA/2 X C57BL/6) F1 female mice. Heterozygotes were interbred to generate homozygotes. Upon arrival at The Jackson Laboratory, the mice were crossed to B6D2F1/J mice (Stock No. 100006) at least once to establish the colony. The mice were then backcrossed to DBA/2J (Stock No. 000671) for at least 5 generations using a marker assisted protocol.