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 Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation N?+N1F2pN1 Generation Definitions   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.

When bred to a strain expressing Cre recombinase in chrondocytes (see Stock No. 003554 for example), this mutant mouse strain may be useful in studies of cartilage and bone development.

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

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.

Mbtps1^tm1Jdh/Mbtps1^tm1Jdh Tg(Col2a1-cre)1Bhr/0

        involves: 129S6/SvEvTac * C57BL/6 * SJL   (conditional)

• mortality/aging
• complete neonatal lethality
  • mice die during or shortly after birth   (MGI Ref ID J:135374)
• skeleton phenotype
• abnormal skeleton morphology
  • all skeletal elements are smaller than in wild-type mice   (MGI Ref ID J:135374)
• • abnormal basicranium morphology
    • the chondo-cranial base is shortened compared to in wild-type mice   (MGI Ref ID J:135374)
  • abnormal skeleton development
    • at E14.5, endochondral chondrocytes fail to exhibit a change from proliferation to hypertrophic cells unlike in wild-type mice   (MGI Ref ID J:135374)
  • • abnormal bone mineralization
      • mice exhibit abnomal mineralization of hypertrophic chondrocytes in long bones that is associated with increased chondrocyte apoptosis unlike in wild-type mice   (MGI Ref ID J:135374)
    • abnormal long bone hypertrophic chondrocyte zone
      • at E15.5, mice lack an organized hypertrophic zone unlike wild-type mice   (MGI Ref ID J:135374)
      • differentiation of hypertrophic chonndrocytes is incomplete   (MGI Ref ID J:135374)
      • chondrocytes exhibit abnormal mineralization that precludes vascularization of skeletal elements   (MGI Ref ID J:135374)
    • chondrodystrophy   (MGI Ref ID J:135374)
    • failure of endochondral bone ossification   (MGI Ref ID J:135374)
  • short mandible   (MGI Ref ID J:135374)
  • short maxilla   (MGI Ref ID J:135374)
  • small cranium   (MGI Ref ID J:135374)
• abnormal skeleton physiology
  • the skull bones exhibit increased sensitivity to potassium hydroxide compared to wild-type bones   (MGI Ref ID J:135374)
• growth/size phenotype
• abnormal chest morphology
  • the chest cavity is small and compresses the internal organs into the abdominal cavity unlike in wild-type mice   (MGI Ref ID J:135374)
• decreased birth body size
  • mice are small at birth   (MGI Ref ID J:135374)
• distended abdomen   (MGI Ref ID J:135374)
• craniofacial phenotype
• abnormal basicranium morphology
  • the chondo-cranial base is shortened compared to in wild-type mice   (MGI Ref ID J:135374)
• protruding tongue
  • mice are born with protruding tongues   (MGI Ref ID J:135374)
• short mandible   (MGI Ref ID J:135374)
• short maxilla   (MGI Ref ID J:135374)
• small cranium   (MGI Ref ID J:135374)
• digestive/alimentary phenotype
• protruding tongue
  • mice are born with protruding tongues   (MGI Ref ID J:135374)
• limbs/digits/tail phenotype
• abnormal limb morphology
  • the orientation of the limbs is skewed likely due to abnormal articular joint development   (MGI Ref ID J:135374)
• • abnormal long bone hypertrophic chondrocyte zone
    • at E15.5, mice lack an organized hypertrophic zone unlike wild-type mice   (MGI Ref ID J:135374)
    • differentiation of hypertrophic chonndrocytes is incomplete   (MGI Ref ID J:135374)
    • chondrocytes exhibit abnormal mineralization that precludes vascularization of skeletal elements   (MGI Ref ID J:135374)

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
      Mutagenesis and Transgenesis: Cre-lox System
      Mutagenesis and Transgenesis: transcriptional activation
Reproductive Biology Research
      Cre-lox System

Genes & Alleles

Gene & Allele Information provided by MGI

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; 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, Melt Curve Analysis
Mbtps1^tm1Jdh, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

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; DeLassus E; Hayashi S; Sandell LJ. 2011. Site-1 protease is essential to growth plate maintenance and is a critical regulator of chondrocyte hypertrophic differentiation in postnatal mice. J Biol Chem 286(33):29227-40. [PubMed: 21652717]  [MGI Ref ID J:175925]

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

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, RG10/RG30.

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 Supply Notes

• This strain is included in the Induced Mutant Resource Colony collection.
• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	None Available
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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.

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