Strain Name:

B6.Cg-Col1a1tm2(tetO-LIN28B)Gqda/J

Stock Number:

023911

Availability:

Under Development for Cryo

Estimated Available for Distribution Date: 05-MAY-14
Use Restrictions Apply, see Terms of Use
Register Interest
These transgenic mice express human LIN28B under the regulatory control of a Col1a1 (collagen, type I, alpha 1)-driven tetO promoter and are useful in studies of metabolism.

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; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Mating SystemHeterozygote x Heterozygote         (Female x Male)   02-JAN-14
Specieslaboratory mouse
 
Donating Investigator George Q. Daley,   Children's Hospital Boston

Description
Lin28b (lin-28 homolog B (C. elegans)) is highly expressed during normal embryogenesis and is upregulated in some cancers to potently and selectively block the maturation of let-7 (Mirlet7) tumor suppressor microRNAs.

These targeted mutant mice carry human LIN28B under the regulatory control of a Col1a1 (collagen, type I, alpha 1)-driven tetO promoter. LIN28B expression can be regulated in progeny derived from crosses with rtTA or tTA mice.

When crossed with Gt(ROSA)26Sor M2-rtTA strain (see Stock No. 006965), expression is not leaky and mice not induced with the tetracycline analog doxycycline (dox) exhibit no growth or glucose phenotypes. After 14 days of treatment with dox, high levels of LIN28B are induced and mature let-7's are repressed in metabolically important organs (e.g. gut, spleen, liver), resulting in hypoglycemia. Compound mutant mice are resistant to diet-induced obesity and diabetes, and exhibit sensitivity to insulin and enhanced glucose tolerance.

Development
A targeting vector containing a splice acceptor, 2 polyadenylation sequences, a tetracycline operator, flag-tagged human LIN28B cDNA, and an SV40 polyadenylation signal within 3'UTR of the mouse Col1a1 gene was introduced to (C57BL/6 x 129S4/SvJae)F1-derived v6.5 embryonic stem (ES) cells containing M2-rtTA (optimized rtTA) targeted to the Gt(ROSA)26Sor locus promoter (see Stock No. 006965 for mutation details). Resultant chimeric males were crossed with outbred CD1 females. The Gt(ROSA)26Sor M2-rtTA mutation was bred away from this strain. The line was backcrossed to C57BL/6 for 8 generations by the donating lab.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls

Related Strains

View Strains carrying other alleles of Col1a1     (18 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Caffey Disease   (COL1A1)
Collagen, Type I, Alpha-1; COL1A1   (COL1A1)
Ehlers-Danlos Syndrome, Type I   (COL1A1)
Ehlers-Danlos Syndrome, Type VII, Autosomal Dominant   (COL1A1)
Osteogenesis Imperfecta, Type I   (COL1A1)
Osteogenesis Imperfecta, Type II   (COL1A1)
Osteogenesis Imperfecta, Type III   (COL1A1)
Osteogenesis Imperfecta, Type IV   (COL1A1)
Osteoporosis   (COL1A1)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype relates to a compound genotype created using this strain.
Contact JAX® Services jaxservices@jax.org for customized breeding options.

Col1a1tm2(tetO-LIN28B)Gqda/Col1a1+ Gt(ROSA)26Sortm1(rtTA*M2)Jae/Gt(ROSA)26Sor+

        involves: 129S4/SvJae * C57BL/6 * CD-1
  • growth/size/body phenotype
  • decreased susceptibility to diet-induced obesity
    • following doxycycline treatment mice gain less weight when fed a high fat diet compared to wild-type mice   (MGI Ref ID J:177113)
  • homeostasis/metabolism phenotype
  • decreased susceptibility to diet-induced obesity
    • following doxycycline treatment mice gain less weight when fed a high fat diet compared to wild-type mice   (MGI Ref ID J:177113)
  • hypoglycemia
    • following doxycycline treatment average fasting glucose is less than 50 mg/dL   (MGI Ref ID J:177113)
  • improved glucose tolerance
    • following doxycycline treatment on a normal or high fat diet   (MGI Ref ID J:177113)
  • increased insulin sensitivity
    • following doxycycline treatment   (MGI Ref ID J:177113)
View Research Applications

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

Diabetes and Obesity Research
Obesity Without Diabetes
      diet-induced, resistant

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Col1a1tm2(tetO-LIN28B)Gqda
Allele Name targeted mutation 2, George Q Daley
Allele Type Targeted (knock-in)
Common Name(s) iLIN28B;
Strain of Origin(C57BL/6 x 129S4/SvJae)F1
Gene Symbol and Name Col1a1, collagen, type I, alpha 1
Chromosome 11
Gene Common Name(s) COLIA1; Col1a-1; Cola-1; Cola1; Moloney leukemia virus 13; Mov-13; OI4;
General Note The allele was made in KH2 cells that carry Gt(ROSA)26Sortm1(rtTA*M2)Jae and Col1a1tm13(neo/hygro*)Jae.
Molecular Note RMCE on KH2 cells inserted a construct, which contains (5' to 3') a splice acceptor, 2 polyadenylation sequence, tetracycline operator, a flag-tagged human LIN28B cDNA, and an SV40 polyadenylation signal, into the 3'UTR. No expression of the inserted gene is detected in the absence of doxycycline treatment. [MGI Ref ID J:177113]

Genotyping

Genotyping Information

Genotyping Protocols

Col1a1tm1(tetO-Lin28a)Gqda, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Zhu H; Shyh-Chang N; Segre AV; Shinoda G; Shah SP; Einhorn WS; Takeuchi A; Engreitz JM; Hagan JP; Kharas MG; Urbach A; Thornton JE; Triboulet R; Gregory RI; Altshuler D; Daley GQ. 2011. The Lin28/let-7 Axis Regulates Glucose Metabolism. Cell 147(1):81-94. [PubMed: 21962509]  [MGI Ref ID J:177113]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & HusbandryHomozygous and heterozygous tetO-LIN28B are viable and fertile.
Mating SystemHeterozygote x Heterozygote         (Female x Male)   02-JAN-14

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


 

This strain is currently Under Development for Cryo.
Estimated Available for Distribution Date: 05-MAY-14

Please note: You may now place orders for this strain although it is not yet ready for distribution. Estimated available for distribution dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for distribution depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

Payment Terms and Conditions

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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.
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