Overview

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.

Donating Investigator

Gregory Cox, The Jackson Laboratory

Genetic overview

Genetic Background	Generation
	N10+F21 (2017-10-18 00:00:00)

Tg(Ttn-Ighmbp2)108Cx

Allele Type
Transgenic (Inserted expressed sequence)

Ighmbp2^nmd-2J

Allele Type	Gene Symbol	Gene Name
Spontaneous	Ighmbp2	immunoglobulin mu binding protein 2

View Genetics

Research Applications

Neurobiology Research
Mouse/Human Gene Homologs

View All Research Applications

Base Price

Starting at:

$179.88 Domestic price for female

470.89 Domestic price for breeder pair

View Price List

Details

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).

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 108 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.

Expression Data

Expressed Gene	Ighmbp2, immunoglobulin mu binding protein 2, mouse, laboratory
Site of Expression
Site of Expression

Selected References

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):3179-89PubMed: 16174646 MGI: J:102748

View All References

Genetics

Tg(Ttn-Ighmbp2)108Cx

Allele Symbol: Tg(Ttn-Ighmbp2)108Cx

Allele Name	transgene insertion 108, Gregory A Cox
Allele Type	Transgenic (Inserted expressed sequence)
Allele Synonym(s)	TgMI
Gene Symbol and Name	Tg(Ttn-Ighmbp2)108Cx, transgene insertion 108, Gregory A Cox
Gene Synonym(s)
Promoter	Ttn, titin, mouse, laboratory
Expressed Gene	Ighmbp2, immunoglobulin mu binding protein 2, mouse, laboratory
Strain of Origin	C57BL/6J
Chromosome	UN
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.

Ighmbp2^nmd-2J

Allele Symbol: Ighmbp2^nmd-2J

Allele Name	neuromuscular degeneration 2 Jackson
Allele Type	Spontaneous
Allele Synonym(s)	nmd^2J
Gene Symbol and Name	Ighmbp2, immunoglobulin mu binding protein 2
Gene Synonym(s)
Strain of Origin	BKS.Cg-Dock7^m +/+ Lepr^db/J
Chromosome	19
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).

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Genotype: Ighmbp2^nmd-2J related

Neurobiology Research
- Neurodegeneration
- Spinal Muscular Atrophy (SMA)
- Amyotrophic Lateral Sclerosis (ALS)
Mouse/Human Gene Homologs
- Spinal Muscular Atrophy with Respiratory Distress Type I (SMARD1)

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Ighmbp2^nmd-2J/Ighmbp2^nmd-2J Tg(Ttn-Ighmbp2)108Cx/?
involves: C57BL/6J * C57BLKS/J

behavior/neurological phenotype

abnormal food intake

dysphagia
- difficulty in mastication or deglutition

nervous system phenotype

motor neuron degeneration
- severe skeletal muscle neurogenic atrophy

digestive/alimentary phenotype

dysphagia
- difficulty in mastication or deglutition

enlarged esophagus
- susceptible to mega-esophagus

growth/size/body region phenotype

enlarged esophagus
- susceptible to mega-esophagus

weight loss
- the presence of the transgene does not rescue the weight loss found in nmd-2J homozygotes

mammalian phenotype

cardiovascular system phenotype
- Normal - mean ventricular free-wall thickness is normal

mortality/aging

premature death
- lifespan is longer than that of nmd-2J mutants but shorter than that of wild-type controls and falls partway between the two points

muscle phenotype

muscle degeneration
- resulting from the spinal motor neuron degeneration

References

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):3179-89PubMed: 16174646 MGI: J:102748

Additional - Ighmbp2^nmd-2J related

Additional - Tg(Ttn-Ighmbp2)108Cx related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Genotyping resources and troubleshooting
Mating System
- Tg/0 nmd-2J/+ x +/+ nmd-2J/
Citation
When using the B6.Cg-Ighmbp2^nmd-2J Tg(Ttn-Ighmbp2)108Cx/Cx mouse strain in a publication, please cite the originating article(s) and include JAX stock #006514 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

A6 (Intermediate)

Pricing & Availability

Availability Varies

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Breeder Pair

Sex

Genotype

Price

Female
Male

Cryorecovery - Pricing

Service/Product	Description	Price
	Please inquire

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

Credit for PRODUCTS or SERVICES

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.

Animal Care and Use for SERVICES

Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Selected References

Tg(Ttn-Ighmbp2)108Cx

Allele Symbol: Tg(Ttn-Ighmbp2)108Cx

Ighmbp2nmd-2J

Allele Symbol: Ighmbp2nmd-2J

Disease Terms

Research Areas By Phenotype

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

Genotype: Ighmbp2nmd-2J related

Mammalian Phenotype Terms by Genotype

Genotype: Ighmbp2nmd-2J/Ighmbp2nmd-2J Tg(Ttn-Ighmbp2)108Cx/?involves: C57BL/6J * C57BLKS/J

behavior/neurological phenotype

nervous system phenotype

digestive/alimentary phenotype

growth/size/body region phenotype

mammalian phenotype

mortality/aging

muscle phenotype

References

Additional - Ighmbp2nmd-2J related

Additional - Tg(Ttn-Ighmbp2)108Cx related

Genotyping Protocols

Mating System

Citation

Animal Health Reports

Live Mouse

Breeder Pair

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Ighmbp2^nmd-2J

Allele Symbol: Ighmbp2^nmd-2J

Genotype: Ighmbp2^nmd-2J related

Genotype: Ighmbp2^nmd-2J/Ighmbp2^nmd-2J Tg(Ttn-Ighmbp2)108Cx/?
involves: C57BL/6J * C57BLKS/J

Additional - Ighmbp2^nmd-2J related