Overview

In this strain, a neo cassette replaces exon 2 and the coding region of exon 3 of the cardiotrophin 1 (Ctf1) gene, abolishing gene expression. These mice may be useful for studying the role of cardiotrophin 1 in neurogenesis and metabolism.

Donating Investigator

Michael Sendtner, University of Wuerzburg

Genetic overview

Genetic Background	Generation

Ctf1^tm1Msd

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Ctf1	cardiotrophin 1

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Research Applications

Diabetes and Obesity Research
Neurobiology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

In this ct-1-/- strain, a neo cassette replaces exon 2 and the coding region of exon 3 of the cardiotrophin 1 (Ctf1) gene, abolishing gene expression. CT-1, a member of the gp130 family of cytokines, is highly expressed in embryonic skeletal muscle and promotes the survival of developing motor neurons. Through its activation of phosphatidylinositol 3-kinase, CT-1 acts to regulate fat and glucose metabolism. CT-1 has also been implicated in bone formation and myocardial remodeling. Homozygous mice are viable and fertile. Ct-1-/- mice exhibit increased cell death of developing motoneurons in spinal cord and brainstem in mice between E14 and the first postnatal week. They also have few cortical astrocytes and show reduction in muscle strength. These mice also display decreased energy expenditure, mature-onset obesity, insulin resistance, and hypercholesterolemia.

Development

A targeting vector was designed to replace exon 2 and the complete coding region of exon 3 of the cardiotrophin 1 (Ctf1) gene with a neomycin resistance (neo) cassette in reverse orientation to the gene. The construct was electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and the resulting chimeric males were bred to C57BL/6J females. The donating investigator reports that these ct-1-/- mice were bred for at least 10 generations to C57BL/6J background (see SNP note below). Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 3 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Oppenheim RW; Wiese S; Prevette D; Armanini M; Wang S; Houenou LJ; Holtmann B; Gotz R; Pennica D; Sendtner M. 2001. Cardiotrophin-1, a muscle-derived cytokine, is required for the survival of subpopulations of developing motoneurons. J Neurosci 21(4):1283-91PubMed: 11160399 MGI: J:77294

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Genetics

Ctf1^tm1Msd

Allele Symbol: Ctf1^tm1Msd

Allele Name	targeted mutation 1, Michael Sendtner
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	ct-1 -
Gene Symbol and Name	Ctf1, cardiotrophin 1
Gene Synonym(s)
Strain of Origin	129S2/SvPas
Chromosome	7
Molecular Note	A neomycin selection cassette replaced a genomic fragment spanning exon 2 and the complete coding region of exon 3. In situ hybridization studies on homozygous embryos demonstrated that no detectable transcript is expressed from this allele.

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

type 2 diabetes mellitus

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

abdominal obesity-metabolic syndrome

Research Areas By Phenotype

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

Diabetes and Obesity Research
- Obesity Without Diabetes
  - adult onset
- Insulin Resistance
Neurobiology Research
- Astrocyte Defects
- Muscular Dystrophy
- Metabolic Defects
- Neuromuscular defects
- Neurodegeneration

Mammalian Phenotype Terms by Genotype

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

Genotype: Ctf1^tm1Msd/Ctf1^tm1Msd
involves: C57BL/6

behavior/neurological phenotype

decreased grip strength
- at 4 months of age, homozygotes display a significant reduction in grip strength relative to wild-type littermates
- Normal - however, loss of muscle strength does not result in any other obvious behavioral deficits

nervous system phenotype

motor neuron degeneration
- Normal - however, no significant differences in motoneuron numbers are detected in the lumbar spinal cord at E13.5-E14.5 or in the facial nucleus at E15 relative to wild-type mice
- Normal - in addition, axotomized homozygotes show no significant further loss of motorneurons in the facial nucleus at 2 or 6 months relative to wild-type mice
- in the brachial spinal cord, motoneuron loss is increased by 30% and 40% at P1 and P9, respectively
- in the brainstem nuclei, facial motorneuron loss is increased by 24% and 22% at P1 and P9, respectively, by 20% at 4 weeks, and by 16% and 17% at 3 and 6 months, respectively, while hypoglossal motorneuron loss is increased by 23% at both P1 and P9
- in the lumbar spinal cord, motoneuron loss is increased by 23% and 26% at P1 and P9, respectively
- in the thoracic spinal cord, motoneuron loss is increased by 29% and 43% at P1 and P9, respectively

Genotype: Ctf1^tm1Msd/Ctf1^tm1Msd
B6.Cg-Ctf1

adipose tissue phenotype

increased fat cell size
- adipocyte hypertrophy is seen in mature mutants

increased total body fat amount
- weight gain is mostly due to increased adipose tissue

homeostasis/metabolism phenotype

decreased circulating free fatty acid level
- old obese mutants exhibit lower circulating free fatty acids than controls

decreased energy expenditure
- in 2 month old mutants, energy expenditure is reduced compared to wild-type mice, with differences increasing with age

decreased oxygen consumption
- in 2 month old mutants, oxygen consumption is reduced compared to wild-type mice, with differences increasing with age

enhanced lipolysis
- adipocytes from obese mutants show increased baseline lipolysis and respond poorly to isoproterenol

hyperglycemia
- hyperglycemia is seen from 6 months of age

increased circulating cholesterol level
- hypercholesterolemia is seen from 6 months of age

increased circulating insulin level
- hyperinsulinemia is seen from 6 months of age

increased circulating leptin level
- increase in serum leptin levels in parallel with progression of weight gain

increased respiratory quotient
- respiratory quotient is elevated in mature obese mutants compared to mature wild-type mice

increased susceptibility to diet-induced obesity
- 2 month old mutants fed a high-fat diet for 12 weeks gain more weight and accumulate more epididymal, retroperitoneal, and subcutaneous fat mass than wild-type mice

insulin resistance
- insulin resistance is seen in obese mutants

behavior/neurological phenotype

decreased food intake
- mutants become obese despite reduced food intake from 2-12 months compared to controls

cellular phenotype

abnormal aerobic respiration
- oxygen consumption is reduced in adipocytes from obese mutants

decreased mitochondrial DNA content
- mitochondrial DNA levels are reduced in white adipose tissue, indicating impaired mitochondrial biogenesis

endocrine/exocrine gland phenotype

enlarged pancreatic islets
- pancreatic islet size is increased at 9 and 12 months of age

increased pancreatic islet number
- pancreatic islet number is increased at 9 and 12 months of age

growth/size/body region phenotype

increased susceptibility to diet-induced obesity
- 2 month old mutants fed a high-fat diet for 12 weeks gain more weight and accumulate more epididymal, retroperitoneal, and subcutaneous fat mass than wild-type mice

obese
- mutants develop spontaneous adult-onset obesity, with weight gain first seen starting at 6 months of age

References

Oppenheim RW; Wiese S; Prevette D; Armanini M; Wang S; Houenou LJ; Holtmann B; Gotz R; Pennica D; Sendtner M. 2001. Cardiotrophin-1, a muscle-derived cytokine, is required for the survival of subpopulations of developing motoneurons. J Neurosci 21(4):1283-91PubMed: 11160399 MGI: J:77294

Additional - Ctf1^tm1Msd related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Ctf1
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, homozygous mice may be bred together.
- Additional Breeding and Husbandry Support
Citation
When using the B6.129S2-Ctf1^tm1Msd/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #022355 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

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

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous for Ctf1<tm1Msd>

Related Products and Services

Frozen Mouse Embryo	B6.129S2-Ctf1<tm1Msd>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129S2-Ctf1<tm1Msd>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129S2-Ctf1<tm1Msd>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6.129S2-Ctf1<tm1Msd>/J Frozen Embryo	$3373.50

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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.

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Ctf1tm1Msd

Allele Symbol: Ctf1tm1Msd

Disease Terms

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Ctf1tm1Msd/Ctf1tm1Msdinvolves: C57BL/6

behavior/neurological phenotype

nervous system phenotype

Genotype: Ctf1tm1Msd/Ctf1tm1MsdB6.Cg-Ctf1

adipose tissue phenotype

homeostasis/metabolism phenotype

behavior/neurological phenotype

cellular phenotype

endocrine/exocrine gland phenotype

growth/size/body region phenotype

References

Additional - Ctf1tm1Msd related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Related Products and Services

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

Ctf1^tm1Msd

Allele Symbol: Ctf1^tm1Msd

Genotype: Ctf1^tm1Msd/Ctf1^tm1Msd
involves: C57BL/6

Genotype: Ctf1^tm1Msd/Ctf1^tm1Msd
B6.Cg-Ctf1

Additional - Ctf1^tm1Msd related