Strain Name:

B6.Cg-Ighmbp2nmd-2J Tg(Ttn-Ighmbp2)45Cx/Cx

Stock Number:

006513

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Research Strain

This strain carries the spontaneous mutation neuromuscular degeneration (nmd-2J) and a transgene expressing Ighmbp2 under the control of the muscle-specific titin (Ttn) promoter. The transgene extends lifespan by preventing primary dilated cardiac myopathy despite the presence of neuromuscular degeneration. This strain is useful for studies involving the role of Ighmpb2 in motor neuron disease and human cardiomyopathy.

Description

Strain Information

Type Congenic; Targeted Mutation; Transgenic;
Additional information on Genetically Engineered and Mutant Mice.
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Additional information on Congenic nomenclature.
Mating SystemTg/0 nmd-2J/+ x +/+ nmd-2J/+
Specieslaboratory mouse
GenerationN10+F7 (01-DEC-09)
Generation Definitions
 
Donating Investigator Gregory Cox,   The Jackson Laboratory

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).

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.

Development
A transgenic construct was designed with a full-length Ighmbp2 cDNA under the control of the mouse titin promoter. The construct was introduced into C57BL/6J donor eggs. Founder line 45 was consequently established. Transgenic mice were crossed to the spontaneous mutant B6.BKS-Ighmbp2nmd-2J for two generations to generate transgene positive mice homozygous for the nmd-2J.

Related Strains

View Strains carrying   Ighmbp2nmd-2J     (4 strains)

View Strains carrying other alleles of Ighmbp2     (3 strains)

Strains carrying other alleles of Ttn
006514   B6.Cg-Ighmbp2nmd-2J Tg(Ttn-Ighmbp2)108Cx/Cx
001512   B6C3Fe a/a-Ttnmdm/J
View Strains carrying other alleles of Ttn     (2 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Spinal Muscular Atrophy, Distal, Autosomal Recessive, 1; DSMA1   (IGHMBP2)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Ighmbp2nmd-2J/Ighmbp2nmd-2J Tg(Ttn-Ighmbp2)45Cx/?

        involves: C57BL/6J * C57BLKS/J
  • mortality/aging
  • premature death
    • lifespan is longer than that of nmd-2J mutants but shorter than that of the wild-type controls and falls partway between the two points   (MGI Ref ID J:102748)
  • nervous system phenotype
  • motor neuron degeneration
    • severe skeletal muscle neurogenic atrophy   (MGI Ref ID J:102748)
  • muscle phenotype
  • muscle degeneration
    • resulting from the spinal motor neuron degeneration   (MGI Ref ID J:102748)
  • behavior/neurological phenotype
  • abnormal food intake   (MGI Ref ID J:102748)
    • dysphagia
      • difficulty in mastication or deglutition   (MGI Ref ID J:102748)
  • cardiovascular system phenotype
  • *normal* cardiovascular system phenotype
    • mean ventricular free-wall thickness is normal   (MGI Ref ID J:102748)
  • digestive/alimentary phenotype
  • dysphagia
    • difficulty in mastication or deglutition   (MGI Ref ID J:102748)
  • enlarged esophagus
    • susceptible to mega-esophagus   (MGI Ref ID J:102748)
  • growth/size/body phenotype
  • weight loss
    • the presence of the transgene does not rescue the weight loss found in nmd-2J homozygotes   (MGI Ref ID J:102748)
View Research Applications

Research Applications
This mouse can be used to support research in many areas including:

Ighmbp2nmd-2J related

Neurobiology Research
Amyotrophic Lateral Sclerosis (ALS)
Neurodegeneration
Spinal Muscular Atrophy (SMA)

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Ighmbp2nmd-2J
Allele Name neuromuscular degeneration 2 Jackson
Allele Type Spontaneous
Common Name(s) nmd2J;
Strain of OriginBKS.Cg-Dock7m +/+ Leprdb/J
Gene Symbol and Name Ighmbp2, immunoglobulin mu binding protein 2
Chromosome 19
Gene Common Name(s) AEP; CATF1; HCSA; HMN6; RIPE3b1; SMARD1; SMUBP2; Smbp-2; Smbp2; ZFAND7; immunoglobulin S mu binding protein 2; neuromuscular degeneration; nmd; p110 subunit; sma; spinal muscular atrophy;
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. [MGI Ref ID J:51890]
 
Allele Symbol Tg(Ttn-Ighmbp2)45Cx
Allele Name transgene insertion 45, Gregory A Cox
Allele Type Transgenic (Inserted expressed sequence)
Common Name(s) TgMI;
Strain of OriginC57BL/6J
Expressed Gene Ighmbp2, immunoglobulin mu binding protein 2, mouse, laboratory
Promoter Ttn, titin, mouse, laboratory
Molecular Note A cDNA sequence encoding the full mouse Ighmbp2 was placed under the control of a modified 5.87 kb mouse genomic fragment containing the Ttn promoter, non-coding Ttn exon 1, intron 1, and 30 base pairs of Ttn exon 2 lacking the start codon. Transgene expression was limited to the heart and skeletal muscles as confirmed by RT-PCR expression using Ighmbp2 exon 1. [MGI Ref ID J:102748]
 
 

Genotyping

Genotyping Information


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References

References provided by MGI

Selected Reference(s)

Maddatu TP; Garvey SM; Schroeder DG; Zhang W; Kim SY; Nicholson AI; Davis CJ; Cox GA. 2005. Dilated cardiomyopathy in the nmd mouse: transgenic rescue and QTLs that improve cardiac function and survival. Hum Mol Genet 14(21):3179-89. [PubMed: 16174646]  [MGI Ref ID J:102748]

Additional References

Ighmbp2nmd-2J related

Cook SA; Johnson KR; Bronson RT; Davisson MT. 1995. Neuromuscular degeneration (nmd): a mutation on mouse chromosome 19 that causes motor neuron degeneration. Mamm Genome 6(3):187-91. [PubMed: 7749225]  [MGI Ref ID J:23584]

Cox GA; Mahaffey CL; Frankel WN. 1998. Identification of the mouse neuromuscular degeneration gene and mapping of a second site suppressor allele. Neuron 21(6):1327-37. [PubMed: 9883726]  [MGI Ref ID J:51890]

Grohmann K; Rossoll W; Kobsar I; Holtmann B; Jablonka S; Wessig C; Stoltenburg-Didinger G; Fischer U; Hubner C; Martini R; Sendtner M. 2004. Characterization of Ighmbp2 in motor neurons and implications for the pathomechanism in a mouse model of human spinal muscular atrophy with respiratory distress type 1 (SMARD1). Hum Mol Genet 13(18):2031-42. [PubMed: 15269181]  [MGI Ref ID J:92862]

Krieger F; Elflein N; Ruiz R; Guerra J; Serrano AL; Asan E; Tabares L; Jablonka S. 2013. Fast motor axon loss in SMARD1 does not correspond to morphological and functional alterations of the NMJ. Neurobiol Dis 54:169-82. [PubMed: 23295857]  [MGI Ref ID J:197642]

Maddatu TP; Garvey SM; Schroeder DG; Hampton TG; Cox GA. 2004. Transgenic rescue of neurogenic atrophy in the nmd mouse reveals a role for Ighmbp2 in dilated cardiomyopathy. Hum Mol Genet 13(11):1105-15. [PubMed: 15069027]  [MGI Ref ID J:90418]

Ruiz R; Lin J; Forgie A; Foletti D; Shelton D; Rosenthal A; Tabares L. 2005. Treatment with trkC agonist antibodies delays disease progression in neuromuscular degeneration (nmd) mice. Hum Mol Genet 14(13):1825-37. [PubMed: 15888478]  [MGI Ref ID J:99795]

de Planell-Saguer M; Schroeder DG; Rodicio MC; Cox GA; Mourelatos Z. 2009. Biochemical and genetic evidence for a role of IGHMBP2 in the translational machinery. Hum Mol Genet 18(12):2115-26. [PubMed: 19299493]  [MGI Ref ID J:148546]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           A6

Colony Maintenance

Mating SystemTg/0 nmd-2J/+ x +/+ nmd-2J/+

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $270.25Female or MaleHeterozygous for Ighmbp2nmd-2J, Hemizygous for Tg(Ttn-Ighmbp2)45Cx  
$167.05Female or MaleHeterozygous for Ighmbp2nmd-2J, Noncarrier  
Price per Pair (US dollars $)Pair Genotype
$437.25Heterozygous for Ighmbp2nmd-2J, Hemizygous for Tg(Ttn-Ighmbp2)45Cx x Heterozygous for Ighmbp2nmd-2J, Noncarrier  
$437.25Heterozygous for Ighmbp2nmd-2J, Noncarrier x Heterozygous for Ighmbp2nmd-2J, Hemizygous for Tg(Ttn-Ighmbp2)45Cx  

Standard Supply

Research Strain. Availability determined by The Jackson Laboratory scientist holding the strain.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $351.40Female or MaleHeterozygous for Ighmbp2nmd-2J, Hemizygous for Tg(Ttn-Ighmbp2)45Cx  
$217.20Female or MaleHeterozygous for Ighmbp2nmd-2J, Noncarrier  
Price per Pair (US dollars $)Pair Genotype
$568.50Heterozygous for Ighmbp2nmd-2J, Hemizygous for Tg(Ttn-Ighmbp2)45Cx x Heterozygous for Ighmbp2nmd-2J, Noncarrier  
$568.50Heterozygous for Ighmbp2nmd-2J, Noncarrier x Heterozygous for Ighmbp2nmd-2J, Hemizygous for Tg(Ttn-Ighmbp2)45Cx  

Standard Supply

Research Strain. Availability determined by The Jackson Laboratory scientist holding the strain.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Research Strain. Availability determined by The Jackson Laboratory scientist holding the strain.

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