Description

Strain Information

Former Names B6.Cg-Rptortm2.1Lex/J    (Changed: 05-OCT-11 ) 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 System Homozygote x Homozygote         (Female x Male)   11-DEC-12 Species laboratory mouse Generation N5+F1 (13-JUL-11) Generation Definitions   Donating Investigator David Sabatini,   Whitehead Institute

Description
These Rptor^flox/flox mutant mice possess loxP sites flanking exon 6 of the regulatory associated protein of mTOR (Mechanistic target of rapamycin), complex 1 , Rptor, targeted gene. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. When these mutant mice are bred to C57BL6-Tg(AlbCre)21Mgn (Stock No. 003574) mice, which direct liver-specific expression of Cre, mice exhibit a decrease in liver size yet produce ketones for hours after feeding. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exon 6 deleted in the cre-expressing tissues. This strain may be useful for studying mTOR-dependent regulation of ketogenesis and other cellular processes in response to feeding and fasting.

Development
A targeting vector was designed to insert a loxP site upstream of exon 6 followed by a frt-flanked neomycin (neo) resistance cassette, followed by loxP sites flanking exon 6 of the regulatory associated protein of MTOR (Mechanistic target of rapamycin), complex 1 (Rptor) gene. The construct was electroporated into 129/SvEv-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into BALB/c blastocysts and resulting chimeric mice were bred to C57BL/6 mice. Heterozygous offspring were bred with Flp transgenic mice on a 129 background to delete the neo cassette, and progeny were crossed to remove the Flp-expressing transgene, resulting in a colony homozygous for the floxed-Rptor (Rptor^flox/flox) allele. The donating investigator reports that these mice were backcrossed to C57BL/6 (see SNP note below) at least 4 generations. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J inbred mice (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, 1 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 Information

	Control
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Rptor

013191

B6.129S5-Rptortm1Lex/J

View Strains carrying other alleles of Rptor     (1 strain)

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

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.

Rptor^tm1.1Dmsa/Rptor^tm1.1Dmsa Tg(Alb-cre)21Mgn/0

        involves: 129S/SvEv * C57BL/6 * DBA   (conditional)

• liver/biliary system phenotype
• abnormal hepatocyte morphology
  • decrease in hepatocyte size   (MGI Ref ID J:167208)
• abnormal liver physiology
  • decrease in liver protein content   (MGI Ref ID J:167208)
  • fasting does not decrease the size of the liver, unlike in controls   (MGI Ref ID J:167208)
• small liver
  • about a 40% decrease in liver mass compared to controls   (MGI Ref ID J:167208)
• homeostasis/metabolism phenotype
• increased circulating ketone body level
  • at early times after refeeding compared to wild-type controls   (MGI Ref ID J:167208)
  • feeding mice sodium octanoate after a fast results in prolonged elevation of ketone levels   (MGI Ref ID J:167208)
  • aged mice do not display a reduction in ketone production during fasting unlike in aged wild-type controls   (MGI Ref ID J:167208)

View Research Applications

Research Applications

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

Developmental Biology Research
Internal/Organ Defects
      liver

Research Tools
Cre-lox System
      loxP-flanked Sequences

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Rptortm1.1Dmsa
Allele Name		targeted mutation 1.1, David M Sabatini
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		RaploxP;
Strain of Origin		129S/SvEv
Gene Symbol and Name		Rptor, regulatory associated protein of MTOR, complex 1
Chromosome		11
Gene Common Name(s)		4932417H02Rik; KOG1; Mip1; RGD1311784; RIKEN cDNA 4932417H02 gene; Rap; mKIAA1303; raptor;
Molecular Note		Exon 6 was flanked by 5' and 3' LoxP sites located 111 bp upstream and 547 bp downstream, respectively, and an FRT flanked neo cassette was inserted via homologous recombination. The neo cassette was removed by flp mediated recombination. [MGI Ref ID J:167208]

Genotyping

Genotyping Information

Genotyping Protocols

Rptor^tm2.1Lex, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Peterson TR; Sengupta SS; Harris TE; Carmack AE; Kang SA; Balderas E; Guertin DA; Madden KL; Carpenter AE; Finck BN; Sabatini DM. 2011. mTOR Complex 1 Regulates Lipin 1 Localization to Control the SREBP Pathway. Cell 146(3):408-20. [PubMed: 21816276]  [MGI Ref ID J:174681]

Sengupta S; Peterson TR; Laplante M; Oh S; Sabatini DM. 2010. mTORC1 controls fasting-induced ketogenesis and its modulation by ageing. Nature 468(7327):1100-4. [PubMed: 21179166]  [MGI Ref ID J:167208]

Additional References

Rptor^tm1.1Dmsa related

Kalaitzidis D; Sykes SM; Wang Z; Punt N; Tang Y; Ragu C; Sinha AU; Lane SW; Souza AL; Clish CB; Anastasiou D; Gilliland DG; Scadden DT; Guertin DA; Armstrong SA. 2012. mTOR complex 1 plays critical roles in hematopoiesis and Pten-loss-evoked leukemogenesis. Cell Stem Cell 11(3):429-39. [PubMed: 22958934]  [MGI Ref ID J:193428]

Wan M; Leavens KF; Saleh D; Easton RM; Guertin DA; Peterson TR; Kaestner KH; Sabatini DM; Birnbaum MJ. 2011. Postprandial hepatic lipid metabolism requires signaling through Akt2 independent of the transcription factors FoxA2, FoxO1, and SREBP1c. Cell Metab 14(4):516-27. [PubMed: 21982711]  [MGI Ref ID J:177644]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice may be bred together.
Mating System	Homozygote x Homozygote         (Female x Male)   11-DEC-12

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

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

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.

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.

---

Ordering Information
JAX^® Mice
Surgical and Preconditioning Services
JAX^® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries regarding Terms of Use

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

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"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "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 the 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 or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

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 and PRODUCTS 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.