Strain Name:

B6.BKS-Ighmbp2nmd-2J/J

Stock Number:

002521

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Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names B6.BKS Ighmbp2nmd-2J/J    (Changed: 14-NOV-05 )
B6.BKS-Ighmbp2nmd-2J/+    (Changed: 15-DEC-04 )
B6.Bks-m db x 8762J    (Changed: 15-DEC-04 )
Type Congenic; Mutant Strain;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse

Appearance
black, affected
Related Genotype: a/a Ighmbp2nmd-2J/Ighmbp2nmd-2J

black, unaffected
Related Genotype: a/a Ighmbp2nmd-2J/+ or a/a ?/+

Description

Motor neuron diseases like amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) are typified by the degeneration of alpha motor neurons in the spinal cord that subsequently leads to muscle atrophy. The nature of such neuromuscular disorders appears to be complex but spontaneous mouse mutants are helping to pinpoint critical genetic variables. The mouse neuromuscular degeneration nmd mutant mice express an autosomal recessive neurological disease where motor neurons degenerate causing the skeletal muscle fibers to atrophy. Behaviorally, these mice are easily identifiable by the second postnatal week. The hindlimbs are dorsally contracted and their locomotor activity is impaired, but balance is not adversely affected. They cannot extend their legs to stand erect or assume full posture on all four limbs. Homozygotes clench their hindlimbs when picked up by the tail and they are unable to grasp a cage cover when held against it. They can maintain proper balance, however, and do not circle, bob their heads, or fall over sideways. Paralysis usually begins in the hindlimbs and later develops in the forelimbs as the disease progresses. Most homozygous mutants die by 3.5-4 weeks of age. Heterozygotes are phenotypically and histologically normal.

The mutant phenotype is very similar to that seen in the human diseases ALS and SMA. The pathology displayed by the degenerating neurons in both species appears similar in that the affected cells seem to "fade away", or stain more lightly for hematoxylin and eosin (H&E) and luxol fast blue-cresylecht violet (LFB-CV). The "fading away" neurons are not swollen, rather the cytoplasmic and nuclear organelles, while normal in structure, appear less densely packed. The populations of motor neurons that are most highly affected by the mouse nmd alleles are those found in the lumbar region, whereas the neurons in the thoracic and cervical spinal cord regions appear primarily normal. Degenerating alpha motor neurons are also found in the sympathetic chain. The muscle fiber lesions contain a mixture of tiny muscle fibers and normally sized fibers. Compared to the proximal muscle groups, the distal musculature of the forelimbs and hindlimbs contain more severe atrophic lesions with adipose tissue abnormally appearing in some instances. The pathology appears limited to neuromuscular aspects since inflammatory and gliotic responses to the lesions are not detected. The overall pattern of muscle denervation and atrophy appears to be random. Finally, it is not clear why the motor neurons are selectively sensitive to the significantly reduced levels of IGHMBP2 given that this DNA binding protein is widely expressed across many cell types. (Cook et al., 1995; Cox et al., 1998; Schmalbruch et al., 1991; Grohmann et al., 2001; Mizuta et al., 1993; Chen et al., 1997; Zhang et al., 1999).

Development
The Ighmbp2nmd-2J/Ighmbp2nmd-2J mice arose spontaneously in the BKS.Cg-m +/+ Leprdb (Stock No. 000642) strain at The Jackson Laboratory Mouse Mutant Resource in 1987. These were backcrossed 11 generations to C57BL/6J. At N12, embryos were frozen from male heterozygotes crossed to female C57BL/6J.

Control Information

  Control
   Untyped from the colony
 
  Considerations for Choosing Controls

Related Strains

View Strains carrying   Ighmbp2nmd-2J     (4 strains)

View Strains carrying other alleles of Ighmbp2     (4 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).
Spinal Muscular Atrophy, Distal, Autosomal Recessive, 1; DSMA1
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Ighmbp2nmd-2J/Ighmbp2nmd-2J

        B6.BKS-Ighmbp2nmd-2J/J
  • mortality/aging
  • premature death
    • at 62 days for males and 76 days for females   (MGI Ref ID J:90418)
    • maximum life span is 138 days for females   (MGI Ref ID J:90418)
  • cardiovascular system phenotype
  • abnormal cardiovascular system physiology   (MGI Ref ID J:90418)
    • abnormal impulse conducting system conduction   (MGI Ref ID J:90418)
      • abnormal QRS complex
        • prolonged and attenuated R waves   (MGI Ref ID J:90418)
      • prolonged P wave
        • attenuated, sometimes split   (MGI Ref ID J:90418)
      • prolonged PR interval
        • prolonged P-R interval   (MGI Ref ID J:90418)
    • decreased heart rate   (MGI Ref ID J:90418)
    • decreased systemic arterial systolic blood pressure
      • decreased lower end systolic blood pressure   (MGI Ref ID J:90418)
    • dilated cardiomyopathy
      • as early as 4-6 weeks of age   (MGI Ref ID J:90418)
      • pale, flaccid, enlarged hearts with one or more thrombi   (MGI Ref ID J:90418)
    • increased heart rate variability   (MGI Ref ID J:90418)
  • abnormal heart morphology   (MGI Ref ID J:90418)
    • abnormal heart valve morphology
      • secondary valvular insufficiency   (MGI Ref ID J:90418)
    • abnormal heart ventricle morphology   (MGI Ref ID J:90418)
      • dilated heart ventricle   (MGI Ref ID J:90418)
      • thin ventricular wall   (MGI Ref ID J:90418)
    • abnormal myocardial fiber morphology
      • few desmosomes   (MGI Ref ID J:90418)
      • abnormal intercalated disc morphology
        • attenuated   (MGI Ref ID J:90418)
      • myocardial fiber degeneration
        • degenerating and apoptotic   (MGI Ref ID J:90418)
        • nuclear blebbing   (MGI Ref ID J:90418)
    • cardiac interstitial fibrosis   (MGI Ref ID J:90418)
    • dilated cardiomyopathy
      • as early as 4-6 weeks of age   (MGI Ref ID J:90418)
      • pale, flaccid, enlarged hearts with one or more thrombi   (MGI Ref ID J:90418)
    • dilated heart atrium   (MGI Ref ID J:90418)
    • myocardial necrosis   (MGI Ref ID J:90418)
  • nervous system phenotype
  • abnormal Schwann cell morphology
    • frequently show indications of secondary myelin degeneration   (MGI Ref ID J:92862)
    • sometimes lacking axons   (MGI Ref ID J:92862)
  • abnormal axon morphology
    • vacuolation occurs during the course of myelination or after myelination   (MGI Ref ID J:92862)
    • abnormal cytoskeletons   (MGI Ref ID J:92862)
    • process of myelination normal   (MGI Ref ID J:92862)
  • abnormal innervation pattern to muscle
    • axon numbers in quadriceps nerves significantly decrease with age from 3 weeks on, 40% reduction by 12-14 weeks   (MGI Ref ID J:92862)
  • abnormal neuromuscular synapse morphology
    • denervation of motor endplates increases dramatically as motor neuron degeneration progresses   (MGI Ref ID J:92862)
  • motor neuron degeneration
    • significant neuronal loss by 7 weeks in all lumbar ventral roots examined   (MGI Ref ID J:90418)
    • 56% of L4 motor axons lost   (MGI Ref ID J:90418)
    • numerous dystrophic axons in ventral roots   (MGI Ref ID J:90418)
    • most losses are of large axons   (MGI Ref ID J:90418)
    • 40% loss of small caliber axons   (MGI Ref ID J:90418)
  • muscle phenotype
  • abnormal diaphragm morphology
    • development of diaphragmatic muscle degeneration occurs late, around 8-14 weeks   (MGI Ref ID J:92862)
  • abnormal myocardial fiber morphology
    • few desmosomes   (MGI Ref ID J:90418)
    • abnormal intercalated disc morphology
      • attenuated   (MGI Ref ID J:90418)
    • myocardial fiber degeneration
      • degenerating and apoptotic   (MGI Ref ID J:90418)
      • nuclear blebbing   (MGI Ref ID J:90418)
  • centrally nucleated skeletal muscle fibers
    • centralized nuclei in myocytes   (MGI Ref ID J:90418)
  • dilated cardiomyopathy
    • as early as 4-6 weeks of age   (MGI Ref ID J:90418)
    • pale, flaccid, enlarged hearts with one or more thrombi   (MGI Ref ID J:90418)
  • increased variability of skeletal muscle fiber size
    • variable fiber size   (MGI Ref ID J:90418)
  • muscle degeneration
    • severe diffuse myocyte degeneration and regeneration   (MGI Ref ID J:90418)
  • skeletal muscle fiber atrophy
    • severe muscle wasting and hind limb contracture   (MGI Ref ID J:90418)
  • skeletal muscle interstitial fibrosis
    • and fatty infiltration   (MGI Ref ID J:90418)
  • behavior/neurological phenotype
  • decreased grip strength
    • much shorter latency to fall when suspended from a wire cage top much shorter latence to fall when suspended from a wire cage top much shorter latence to fall when suspended from a wire cage top much shorter latence to fall when suspended from a wire cage top   (MGI Ref ID J:90418)
  • respiratory system phenotype
  • decreased pulmonary respiratory rate
    • reduced breathing rate (bradypnea)   (MGI Ref ID J:90418)
  • pleural effusion   (MGI Ref ID J:90418)
  • pulmonary edema
    • consolidation of lungs   (MGI Ref ID J:90418)
  • growth/size/body phenotype
  • weight loss   (MGI Ref ID J:90418)
  • homeostasis/metabolism phenotype
  • cardiac interstitial fibrosis   (MGI Ref ID J:90418)
  • increased circulating creatine kinase level
    • 3-7 days prior to clearly evident clinical signs of heart disease, total plasma CK and cardiac-specific CK-MB levels in 5- to 9-week-old mice become significantly elevated   (MGI Ref ID J:90418)
  • pleural effusion   (MGI Ref ID J:90418)
  • pulmonary edema
    • consolidation of lungs   (MGI Ref ID J:90418)
  • skeletal muscle interstitial fibrosis
    • and fatty infiltration   (MGI Ref ID J:90418)

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Ighmbp2nmd-2J/Ighmbp2nmd-2J

        BKS.Cg Dock7m +/+ Leprdb-Ighmbp2nmd-2J
  • mortality/aging
  • premature death
    • death usually by 3.5 weeks although survival for several months is possible if left with parents without normal siblings present   (MGI Ref ID J:23584)
  • behavior/neurological phenotype
  • abnormal gait
    • rely on forelimbs to crawl forward, but balance and righting responses are normal   (MGI Ref ID J:23584)
  • abnormal grip strength
    • unable to grasp cage cover when set upon it   (MGI Ref ID J:23584)
  • hindlimb paralysis
    • dorsally contracted hindlimbs cannot be extended to stand erect or assume full posture on four limbs   (MGI Ref ID J:23584)
  • limb grasping
    • clench hindlimbs when picked up by the tail   (MGI Ref ID J:23584)
  • muscle phenotype
  • abnormal masseter muscle morphology
    • atrophic muscle fibers in the masseter   (MGI Ref ID J:23584)
  • abnormal skeletal muscle fiber morphology
    • intermixture of very small muscle fibers with more normal fibers   (MGI Ref ID J:23584)
    • distal musculature of limbs more severely affected but focal areas of muscle degeneration proximally as well   (MGI Ref ID J:23584)
  • abnormal temporalis muscle morphology
    • atrophic muscle fibers in the temporalis muscle   (MGI Ref ID J:23584)
  • nervous system phenotype
  • abnormal innervation pattern to muscle
    • affected alpha motor neurons with pale staining nuclei and perikarya   (MGI Ref ID J:23584)
    • mostly in lumbar region   (MGI Ref ID J:23584)
View Research Applications

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

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

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]

Genotyping

Genotyping Information

Genotyping Protocols

Ighmbp2nmd-2JPYRO, Pyrosequencing


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

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]

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]

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

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & HusbandryHomozygotes die at about weaning age and must have a foster mother sent along with them.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


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

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3300.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $4290.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   Untyped from the colony
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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