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

Type Congenic; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse   Donating Investigator Joseph C Besharse,   Medical College of Wisconsin

Description
Mice homozygous for this Nocturnin (Ccrn4l or Noc) targeted mutation are viable and fertile, with no detectable Noc protein made from the targeted gene. Homozygotes are resistant to diet-induced obesity and remain lean on high-fat diets, with lower body weight and reduced visceral fat. Unlike lean lipodystrophic mouse models, Noc-deficient mice do not have fatty livers (hepatic steatosis) and do not exhibit increased activity or reduced food intake. In addition to changes in glucose tolerance and insulin sensitivity, homozygous mice may also have deficits in lipid metabolism or lipid uptake. Nocturnin-deficient mice may be useful in studying resistance to diet-induced obesity, physiologic rhythms downstream of the circadian clockwork, and post-transcriptional regulation of genes necessary for nutrient uptake, metabolism, and storage.

Development
A targeting vector was designed to replace introns 2-3 and the coding region of exon 3 (which contains most of the protein coding sequence including the catalytic domain) of the targeted gene with a neomycin resistance cassette. The construct was electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric males were bred with C57BL/6J females. Next, mutant mice were backcrossed to C57BL/6J inbred mice for at least 10 generations 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.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Ccrn4l^tm1Bjc/Ccrn4l^tm1Bjc

        B6.129S2-Ccrn4l^tm1Bjc

• homeostasis/metabolism phenotype
• decreased susceptibility to diet-induced obesity
  • mice do not gain weight as much as wild-type when mice are fed a high fat diet   (MGI Ref ID J:122301)
• impaired glucose tolerance
  • on a high fat diet, glucose tolerance is less than wild-type   (MGI Ref ID J:122301)
• increased circulating glucose level
  • when fed a standard diet, circulating glucose level is slightly increased   (MGI Ref ID J:122301)
• increased insulin sensitivity
  • when fed a standard diet, mice have increased insulin sensitivity   (MGI Ref ID J:122301)
  • however, insulin sensitivity after being fed a high fat diet is comparable to that in wild-type   (MGI Ref ID J:122301)
• liver/biliary system phenotype
• decreased susceptibility to hepatic steatosis   (MGI Ref ID J:122301)
• growth/size phenotype
• decreased susceptibility to diet-induced obesity
  • mice do not gain weight as much as wild-type when mice are fed a high fat diet   (MGI Ref ID J:122301)

View Research Applications

Research Applications

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

Cardiovascular Research
Other
      altered fat metabolism
      altered lipoprotein profile

Cell Biology Research
Transcriptional Regulation

Diabetes and Obesity Research
Impaired Insulin Processing
Insulin Receptors and Growth Factors
Insulin Resistance
Obesity Without Diabetes
      diet-induced, resistant

Endocrine Deficiency Research
Adipose Defects

Internal/Organ Research
Adipose Defects

Metabolism Research
Lipid Metabolism

Neurobiology Research
Circadian Rhythms
Metabolic Defects

Research Tools
Diabetes and Obesity Research
Endocrine Deficiency Research
Metabolism Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Ccrn4ltm1Bjc
Allele Name		targeted mutation 1, JC Besharse
Allele Type		Targeted (knock-out)
Common Name(s)		Noc-;
Mutation Made By		Joseph Besharse,   Medical College of Wisconsin
Strain of Origin		129S2/SvPas
ES Cell Line Name		D3
ES Cell Line Strain		129S2/SvPas
Gene Symbol and Name		Ccrn4l, CCR4 carbon catabolite repression 4-like (S. cerevisiae)
Chromosome		3
Gene Common Name(s)		AU043840; CCR4L; Ccr4; Ccrn4lb; NOC; carbon catabolite repression 4 homolog (S. cerevisiae); expressed sequence AU043840; nocturnin;
Molecular Note		The entire coding region of exon 3, which contains most of the protein coding sequence including the catalytic domain, was replaced with a neomycin resistance cassette. Absence of protein was confirmed in mutant liver homogenates. [MGI Ref ID J:122301]

Genotyping

Genotyping Information

Genotyping Protocols

Ccrn41^tm1Bjc, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Green CB; Douris N; Kojima S; Strayer CA; Fogerty J; Lourim D; Keller SR; Besharse JC. 2007. Loss of Nocturnin, a circadian deadenylase, confers resistance to hepatic steatosis and diet-induced obesity. Proc Natl Acad Sci U S A 104(23):9888-93. [PubMed: 17517647]  [MGI Ref ID J:122301]

Additional References

Ccrn4l^tm1Bjc related

Douris N; Kojima S; Pan X; Lerch-Gaggl AF; Duong SQ; Hussain MM; Green CB. 2011. Nocturnin regulates circadian trafficking of dietary lipid in intestinal enterocytes. Curr Biol 21(16):1347-55. [PubMed: 21820310]  [MGI Ref ID J:176001]

Kawai M; Delany AM; Green CB; Adamo ML; Rosen CJ. 2010. Nocturnin suppresses igf1 expression in bone by targeting the 3' untranslated region of igf1 mRNA. Endocrinology 151(10):4861-70. [PubMed: 20685873]  [MGI Ref ID J:165676]

Kawai M; Green CB; Lecka-Czernik B; Douris N; Gilbert MR; Kojima S; Ackert-Bicknell C; Garg N; Horowitz MC; Adamo ML; Clemmons DR; Rosen CJ. 2010. A circadian-regulated gene, Nocturnin, promotes adipogenesis by stimulating PPAR-gamma nuclear translocation. Proc Natl Acad Sci U S A 107(23):10508-13. [PubMed: 20498072]  [MGI Ref ID J:161288]

Niu S; Shingle DL; Garbarino-Pico E; Kojima S; Gilbert M; Green CB. 2011. The circadian deadenylase Nocturnin is necessary for stabilization of the iNOS mRNA in mice. PLoS One 6(11):e26954. [PubMed: 22073225]  [MGI Ref ID J:180997]

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 & Husbandry	When maintaining a live colony, homozygous mice may be bred together.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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See Terms of Use tab for General Terms and Conditions

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.

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