Immunoglobulin mu binding protein 2 (IGHMBP2) is a DNA/RNA helicase implicated in transcriptional regulation and mRNA splicing. Mutations in IGHMBP2 are associated with the degeneration of alpha motor neurons and spinal muscular atrophy (DSMA1, SMARD1, HMN6) as well as dilated cardiac myopathy (DCM) and skeletal myopathy. nmd-2J mutant mice are characterized by a progressive paralysis that begins in the hindlimbs and moves to the forelimbs in the later stages of the disease. Homozygotes initially are identified by contracted hindlimbs and impaired movement beginning at two weeks of age. Mice rarely survive past 4 weeks of age. Combining nmd-2J mice with transgenic mice expressing Ighmbp2 under the control of the rat neuron-specific enolase promoter (Stock No. 003834, TgNI) halts neuromuscular degeneration, but reveals the presence of cardiac myopathy followed by premature death as a result of congestive heart failure (CHF).
In this strain, nmd-2J mice are combined with transgenic mice expressing Ighmbp2 under the control of the muscle-specific titin (Ttn) promoter (TgMI), the transgene extends lifespan by preventing primary DCM despite the presence of neuromuscular degeneration. Transgene founder lines 45 and 108 exhibit similar phenotypes. This strain is useful for studies involving the role of Ighmpb2 in motor neuron disease and human cardiomyopathy.
