Description

Strain Information

Type Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation N?+N1F2pN1   Donating Investigator Jay Horton,   Univ of Texas SW Med Center at Dallas

Description
These mice carry a targeted mutation in which exon 2 of the targeted gene is flanked by loxP sites. A loxP-flanked ("floxed") neomycin resistance cassette also is inserted downstream in intron 2. Homozygotes are viable and fertile, and the floxed gene appears to function normally. When homozygotes are crossed with transgenic strains expressing Cre-recombinase, cre-mediated recombination of the loxP-flanked sequences can result in one of three genotypes: a) deletion of the neo cassette only, leaving a loxP-flanked second exon and unimpaired endogenous gene function. b) Deletion of exon 2 only, leaving a loxP-flanked neo cassette and no endogenous gene function. c) Deletion of both the neo cassette and exon 2, leaving a single loxP site and no endogenous gene function. When these floxed mutant mice are bred to mice carrying the Mx1-cre transgene (for example, Stock No. 003556), liver-specific disruption of the endogenous gene in Mx1-cre positive, floxed homozygotes leads to reduced expression of genes involved in cholesterol and fatty acid synthesis. Germline disruption of the endogenous gene results in early embryonic lethality. These floxed mutant mice may be useful in studies of lipid homeostasis, cholesterol and fatty acid metabolism, and SREBP activation pathways.

Development
A targeting vector was generated containing a single loxP site within intron 1 and a loxP-flanked neomycin resistance cassette within intron 2 of the endogenous gene (loxP-exon2-loxP-Neo-loxP). This construct was electroporated into 129S6/SvEvTac-derived SM-1 embryonic stem (ES) cells. Correctly targeted cells were injected into C57BL/6 blastocysts. Chimeric males were bred to C57BL/6J females and the heterozygous offspring were bred to facilitate the line (S1P^flox). S1P^flox mice were next bred with Mx1-cre transgenic mice on a mixed C57BL/6J;SJL background. Transgenic positive mice also homozygous for the targeted mutation were interbred for an unknown number of generations before arrival at The Jackson Laboratory. Upon arrival, mice were selectively bred for the targeted mutation (and against the transgene), resulting in homozygous Mbtps1 mutant mice.

Control Information

	Control
	None Available
Considerations for Choosing Controls

Additional Web Information

Cre-lox Systems

Phenotype

Phenotype Information

View Research Applications

Research Applications

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

Cardiovascular Research
Other (altered fat metabolism)

Cell Biology Research
Transcriptional Regulation

Endocrine Deficiency Research
Adipose Defects

Metabolism Research
Lipid Metabolism

Research Tools
Cardiovascular Research (Cre-lox System)
Cre-lox System (loxP-flanked Sequences)
Developmental Biology Research (Cre-lox System)
Diabetes and Obesity Research (loxP)
Genetics Research (Mutagenesis and Transgenesis: Cre-lox System)
Genetics Research (Mutagenesis and Transgenesis: transcriptional activation)
Reproductive Biology Research (Cre-lox System)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Mbtps1tm1Jdh
Allele Name		targeted mutation 1, Jay D Horton
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		S1Pf;
Mutation Made By		Jay Horton,   Univ of Texas SW Med Center at Dallas
Strain of Origin		129S6/SvEvTac
ES Cell Line Name		SM1
ES Cell Line Strain		129S6/SvEvTac
Site of Expression		liver
Gene Symbol and Name		Mbtps1, membrane-bound transcription factor peptidase, site 1
Chromosome		8
Gene Common Name(s)		0610038M03Rik; AV003995; KIAA0091; MGC138711; MGC138712; PCSK8; RIKEN cDNA 0610038M03 gene; S1P; SKI-1; expressed sequence AV003995; site-1 protease; subtilisin/kexin isozyme-1;
Molecular Note		A loxP site was inserted into intron 1 and a loxP-flanked neomycin selection cassette was inserted into exon 2. [MGI Ref ID J:72930]

Genotyping

Genotyping Information

Genotyping Protocols

Generic Cre Melt Curve Analysis, MCA, vers. 1
Generic Cre, STD PCR, vers. 1
Mbtps1^tm1Jdh, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Yang J; Goldstein JL; Hammer RE; Moon YA; Brown MS; Horton JD. 2001. Decreased lipid synthesis in livers of mice with disrupted Site-1 protease gene. Proc Natl Acad Sci U S A 98(24):13607-12. [PubMed: 11717426]  [MGI Ref ID J:72930]

Additional References

Mbtps1^tm1Jdh related

Patra D; Xing X; Davies S; Bryan J; Franz C; Hunziker EB; Sandell LJ. 2007. Site-1 protease is essential for endochondral bone formation in mice. J Cell Biol 179(4):687-700. [PubMed: 18025304]  [MGI Ref ID J:135374]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, mice homozygous for the targeted mutation are bred.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	None Available
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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 and Purchasing Information

      Purchasing Information
      JAX^® Mice Orders
      Surgical Services

Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.

For additional 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

Contracts Administration

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

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (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 with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’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, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, 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 The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials 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 The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory 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 The Jackson Laboratory, 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 The Jackson Laboratory, 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 services by The Jackson Laboratory.