B6.Cg-Tg(Eno2-Ighmbp2)90Cx Ighmbp2^nmd-2J/Cx

Stock number: 003834
Research areas: Mouse/Human Gene Homologs, Neurobiology Research

Description

This strain carries the spontaneous mutation neuromuscular degeneration (nmd-2J) and a transgene expressing Ighmbp2 under the control of the neuron-specific rat enolase (Eno2) promoter. The transgene halts neuromuscular degeneration. This strain is useful for studies involving the role of Ighmpb2 in motor neuron disease and human cardiomyopathy.

Detailed description

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). RT-PCR analysis indicates that transgene expression is limited to the central nervous system including forebrain, cerebellum and spinal cord. This strain is useful for studies involving the role of Ighmpb2 in motor neuron disease and human cardiomyopathy.

Development

A transgenic construct was designed with a full-length Ighmbp2 cDNA under the control of the rat enolase 2 promoter. The construct was introduced into C57BL/6J donor eggs. Founder line 90 was consequently established. Transgenic mice were crossed to the spontaneous mutant B6.BKS-Ighmbp2^nmd-2J for two generations to generate transgene positive mice homozygous for the nmd-2J.

Allele

Symbol: Tg(Eno2-Ighmbp2)90Cx
Name: transgene insertion 90, Gregory A Cox
MGI accession ID: MGI:3784996
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(Eno2-Ighmbp2)90Cx
Marker name: transgene insertion 90, Gregory A Cox
Chromosome: UN
Strain of origin: Not Applicable
Expressed genes: Ighmbp2,immunoglobulin mu binding protein 2,mouse, laboratory
Molecular note: A 3.1 kb mouse Ighmbp2 cDNA sequence was placed under the control of a 4 kb sequence containing the rat Eno2 promoter. Transgene expression was limited to the central nervous system as confirmed by RT-PCR expression using primers within exon 1.

Allele

Symbol: Ighmbp2^nmd-2J
Name: neuromuscular degeneration 2 Jackson
MGI accession ID: MGI:1857648
Generation method: Spontaneous
Marker symbol: Ighmbp2
Marker name: immunoglobulin mu binding protein 2
Chromosome: 19
Strain of origin: BKS.Cg-Dock7^m +/+ Lepr^db/J
Molecular note: An A-to-G transition mutation in intron 4 results in the creation of a cryptic splice site and interferes with the normal splicing of the transcript. RT-PCR analysis on RNA derived from various tissues of homozygous mice demonstrated that approximately 20-25% of the transcripts were spliced normally, while 75-80% of the transcripts were spliced aberrantly. This allele also presents with a deletion of one of the two leucine codons at position 362 and 363 in exon 8 (SW:P40694).