Overview

Also Known As:C57BL/6J-Mstn<Ln>/J

The ENU-induced lean (Ln) allele of myostatin (Mstn^Ln) leads to improper splicing and a loss-of-function allele. These Mstn^Ln mutant mice may be useful in studying diabetes, obesity, fat metabolism, protection from obesity-induced insulin resistance and other high fat diet-associated disorders, as well as Duchenne muscular dystrophy.

Donating Investigator

Nicholas Gekakis, San Diego State University

Genetic overview

Genetic Background	Generation

Mstn^lean

Allele Type	Gene Symbol	Gene Name
Chemically induced (ENU)	Mstn	myostatin

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Research Applications

Diabetes and Obesity Research
Neurobiology Research
Cardiovascular Research
Metabolism Research
Endocrine Deficiency Research
Internal/Organ Research
Research Tools

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous for this ENU-induced mutation, called the lean (Ln) allele of myostatin (Mstn^Ln), are viable and fertile. The Mstn^Ln allele alters mRNA splicing and results in an additional larger transcript containing a 128 basepair insert at the junction between exons 2 and 3. This insertion encodes an additional 4 amino acids before a premature stop codon (ASDNX), and is predicted to generate a truncated protein containing the Mstn signal sequence and propeptide, but lacking the ligand portion of the molecule. In addition to this abnormal splicing product, the mRNA from mutant males is also reduced in abundance by approximately 60% compared to wildtype males. When maintained on normal diet, homozygous (Mstn^Ln/Ln) mice exhibit increased muscularity. When maintained on a high fat diet, homozygotes exhibit glucose tolerance, protection against overall insulin resistance, improved muscle and liver insulin sensitivity (with decreased TNFa production), and ameliorated hepatosteatosis. These Mstn^Ln mutant mice may be useful in studying diabetes, obesity, fat metabolism, and other high fat diet-associated disorders, as well as Duchenne muscular dystrophy.

Development

Following multidose N-ethyl-N-nitrosourea (ENU) treatments to induce mutations in founder C57BL/6J mice, a forward genetic screen was utilized to identify a family of mice that remained lean with low insulin despite high fat feeding. The lean phenotype was mapped to a region of chromosome 1 containing the myostatin (Mstn) gene. Sequencing of this gene identified a T->C transition in the second intron two basepairs downstream of exon 2 (a splice donor position conserved in almost all vertebrate introns). Mice harboring this ENU-induced mutation, called the lean (Ln) allele of Mstn (Mstn^Ln), were maintained on a C57BL/6J genetic background (with approximately two backcrosses to C57BL/6J) prior to arrival at The Jackson Laboratory. Upon arrival, mutant mice were bred with C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony. Of note, the donating investigator reports that there may likely be other ENU-induced mutations present because these mice we not extensively backcrossed to C57BL/6J mice.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Wilkes JJ; Lloyd DJ; Gekakis N. 2009. Loss-of-function mutation in myostatin reduces tumor necrosis factor alpha production and protects liver against obesity-induced insulin resistance. Diabetes 58(5):1133-43PubMed: 19208906 MGI: J:146513

View All References

Genetics

Mstn^lean

Allele Symbol: Mstn^lean

Allele Name	lean
Allele Type	Chemically induced (ENU)
Allele Synonym(s)	Mstn^Ln
Gene Symbol and Name	Mstn, myostatin
Gene Synonym(s)
Strain of Origin	C57BL/6J
Chromosome	1
Molecular Note	Following multidose N-ethyl-N-nitrosourea (ENU) treatments to induce mutations in founder C57BL/6J mice, a T->C transition was found in the second intron two base pairs downstream of exon 2 (a splice donor position conserved in almost all vertebrate introns) in the myostatin (Mstn) gene.
Mutations Made By	Nicholas Gekakis, San Diego State University

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Diabetes and Obesity Research
- Insulin Receptors and Growth Factors
- Obesity Without Diabetes
  - diet-induced, resistant
- Insulin Resistance
- Hyperinsulinemia
- Impaired Insulin Processing
Neurobiology Research
- Muscular Dystrophy
  - Duchenne type
- Metabolic Defects
Cardiovascular Research
- Other
  - altered lipoprotein profile
  - altered fat metabolism
Metabolism Research
- Lipid Metabolism
Endocrine Deficiency Research
- Adipose Defects
Internal/Organ Research
- Adipose Defects
Research Tools
- Diabetes and Obesity Research
- Endocrine Deficiency Research
- Metabolism Research

Mammalian Phenotype Terms by Genotype

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

Genotype: Mstn^lean/Mstn^lean
C57BL/6J-Mstn

homeostasis/metabolism phenotype

decreased adiponectin level
- in chow-fed homozygotes, adiponectin levels are 2-3 fold lower than controls; HFD-fed males display decreased adiponectin levels whereas HFD-fed females showed a trend toward increased levels compared to heterozygous controls

decreased circulating glucose level
- females have lower basal glucose levels than than heterozygous or wild-type littermates

abnormal glucose homeostasis
- Normal - basal GDR is similar between HFD-fed homozygotes and heterozygotes
- in HFD-fed mutants, glucose disposal rate (GDR) upon insulin stimulation is enhanced 200 to 400% compared to HFD-fed heterozygotes

decreased circulating tumor necrosis factor level
- levels are reduced about 40% in HFD-fed males compared to HFD-fed heterozygous males

decreased circulating insulin level
- females and males display lower basal insulin levels than heterozygous or wild-type littermates
- HFD-fed males and females have 3.5 and 2.5-fold lower plasma insulin levels than heterozygous or wild-type controls

abnormal gluconeogenesis
- hepatic glucose production (HPG) is enhanced by 200-400% in HFD-fed homozygotes compared to heterozygotes
- Normal - basal HPG is similar between HFD-fed homozygotes and heterozygotes

increased insulin sensitivity
- allenge
- in response to direct insulin challenge, HFD-fed males have lower blood glucose levels at 20, 40 and 60 minutes compared to heterozygous males; HFD-fed females have lower blood glucose levels than heterozygous females at 60 and 80 minutes after insulin challenge
- whole-body insulin sensitivity is maintained in HFD-fed homozygotes at 10-11 months of age

decreased circulating cholesterol level
- HFD-fed homozygous males have 15-20% lower plasma cholesterol levels than HFD-fed heterozygous or wild-type controls; no difference was observed in HFD-fed female homozygotes

decreased circulating leptin level
- leptin levels in HFD-fed males and females are decreased 3.4- and 9.7-fold compared to HFD-fed controls

abnormal circulating tumor necrosis factor level
- male homozygotes have higher plasma TNF alpha levels than females

decreased circulating triglyceride level
- HFD-fed homozygous males have 15-20% lower plasma triglyceride levels than HFD-fed heterozygous or wild-type controls; no difference was observed in HFD-fed female homozygotes

improved glucose tolerance
- plasma insulin levels after glucose loading are markedly reduced after glucose loading in HFD-fed mice compared to HFD-fed heterozygous controls

insulin resistance
- HFD-fed males and females show improved insulin resistance compared to HFD-fed heterozygous controls

adipose tissue phenotype

decreased percent body fat/body weight
- at 4 months, males have a signicantly lower amount of fat mass than females
- mice remain lean with high fat feeding, in contrast than heterozygous or wild-type littermates; 4-month-old mice weaned onto a high fat diet (HFD) have lower fat mass than heterozygous or wild-type littermates

decreased epididymal fat pad weight
- on a HFD, 10-11 month-old mutant fat pads weigh 3-4-fold less than HFD-fed heterozygotes

immune system phenotype

decreased circulating tumor necrosis factor level
- levels are reduced about 40% in HFD-fed males compared to HFD-fed heterozygous males

abnormal circulating tumor necrosis factor level
- male homozygotes have higher plasma TNF alpha levels than females

liver/biliary system phenotype

decreased susceptibility to hepatic steatosis
- livers of 10-11 month old HFD-fed homozygotes show no evidence of hepatic steatosis whereas livers of HFD-fed heterozygotes exhibit large vacuoles and lipid droplets

decreased susceptibility to diet-induced hepatic steatosis
- livers of 10-11 month old HFD-fed homozygotes show no evidence of hepatic steatosis whereas livers of HFD-fed heterozygotes exhibit large vacuoles and lipid droplets

muscle phenotype

increased gastrocnemius weight
- gastrocnemius muscle weighs 1.4-fold more than that of HFD-fed heterozygotes

increased quadriceps weight
- quadriceps weigh 1.4-fold more than those of HFD-fed heterozygotes

growth/size/body region phenotype

increased lean body mass
- male and female animals fed a high fat diet increase total lean by mass by 10-20% compared to mice maintained on a normal chow diet
- at 4 months, males have a greater amount of lean mass than females
- 4-month-old mice weaned onto a high fat diet have significantly higher lean mass than heterozygous or wild-type littermates

decreased body weight
- at 10-11 months of age, high fat diet (HFD)-fed homozygotes have lower average weight (42.0g) compared to HFD-fed heterozygous controls (51.5g)

References

Wilkes JJ; Lloyd DJ; Gekakis N. 2009. Loss-of-function mutation in myostatin reduces tumor necrosis factor alpha production and protects liver against obesity-induced insulin resistance. Diabetes 58(5):1133-43PubMed: 19208906 MGI: J:146513

Additional - Mstn^lean related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- End Point Analysis:Mstn-EP
- Pyrosequencing:Mstn
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, homozygous mice may be bred.
- Additional Breeding and Husbandry Support
Citation
When using the C57BL/6J-Mstn^lean/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #009345 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
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Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
> >	Heterozygous for Mstn<lean>

Related Products and Services

Frozen Mouse Embryo	C57BL/6J-Mstn<lean>/J	$2595.00
Frozen Mouse Embryo	C57BL/6J-Mstn<lean>/J	$2595.00
Frozen Mouse Embryo	C57BL/6J-Mstn<lean>/J	$3373.50
Frozen Mouse Embryo	C57BL/6J-Mstn<lean>/J	$3373.50

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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

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Questions about Terms of Use

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:C57BL/6J-Mstn<Ln>/J

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Mstnlean

Allele Symbol: Mstnlean

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Mstnlean/MstnleanC57BL/6J-Mstn

homeostasis/metabolism phenotype

adipose tissue phenotype

immune system phenotype

liver/biliary system phenotype

muscle phenotype

growth/size/body region phenotype

References

Additional - Mstnlean 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

Additional Use Restrictions Apply

Licensing Information

Mstn^lean

Allele Symbol: Mstn^lean

Genotype: Mstn^lean/Mstn^lean
C57BL/6J-Mstn

Additional - Mstn^lean related