Overview

Also Known As:mPepT1^-/- huPepT1

huPEPT1 mice express human SLC15A1 (or PEPT1) on a mouse Slc15a1 deficient background. SLC15A1 functions as an intestinal peptide transporter. These mice may be used as a humanized mouse model for studying prodrug absorption and disposition.

Donating Investigator

David E. Smith, University of Michigan

Genetic overview

Genetic Background	Generation

Slc15a1^tm1Dgen

Allele Type	Gene Symbol	Gene Name
Targeted (Reporter, Null/Knockout)	Slc15a1	solute carrier family 15 (oligopeptide transporter), member 1

Tg(SLC15A1)1Dsmi

Allele Type
Transgenic (Inserted expressed sequence, Humanized sequence)

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Research Applications

Research Tools

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Details

Detailed Description

SLC15A1 (solute carrier family 15 (oligopeptide transporter), member 1 or PEPT1) encodes a high-capacity, low-affinity proton-coupled oligopeptide transporter expressed in all regions of the small intestine and specifically at the apical side of enterocytes. SLC15A1 also has low, but measurable expression in the proximal and distal segments of the colon. SLC15A1 is involved in the uptake of di/tripeptides , ACE inhibitors, β-lactam antibiotics and other prodrugs (valacyclovir, zanamivir, etc) from the intestinal lumen. Prodrugs are converted from inactive to pharmacologically active drugs when metabolized. In this case, the relevant prodrugs contain an added chemical promoiety that confers Pept1-mediated transport upon the entire molecule allowing for enhanced intestinal absorption. huPEPT1 mice express human SLC15A1 (or PEPT1) on a mouse Slc15a1 deficient background. Mice homozygous for the knock-out allele and hemizygous for the transgene are viable and fertile with no obvious phenotype. These mice may be used as a humanized mouse model for studying prodrug absorption and disposition.

Development

The human bacterial artificial chromosome (BAC) RP11-782G13 containing the human SLC15A1 (or PEPT1) gene including 5' regulatory elements, coding area, and 3' regulatory elements was introduced by pronuclear injection into fertilized one-cell embryos from females homozygous for Slc15a1^tm1Dgen on the C57BL/6NCrl congenic background (B6N.129P2-Slc15a1^tm1Dgen). Founder mice were bred to C57BL/6 inbred mice. The donating investigator indicates that the founder contains one copy of the human BAC.

The Slc15a1^tm1Dgen knockout allele was generated using 129P2/OlaHsd embryonic stem cells. Chimeric males were crossed to C57BL/6 and progeny backcrossed for 8 generations to C57BL/6NCrl. The targeting construct used an IRES-lacZ-neomycin selection cassette to replace amino acid residues 16-24.

Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6NJ oocytes (Stock No. 005304).

Control Suggestions

Wild-type from the colony
005304 C57BL/6NJ

Additional Information

Considerations for Choosing Controls

Selected References

Hu Y; Xie Y; Wang Y; Chen X; Smith DE. 2014. Development and characterization of a novel mouse line humanized for the intestinal peptide transporter PEPT1. Mol Pharm 11(10):3737-46PubMed: 25148225 MGI: J:273387

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Genetics

Slc15a1^tm1Dgen

Allele Symbol: Slc15a1^tm1Dgen

Allele Name	targeted mutation 1, Deltagen
Allele Type	Targeted (Reporter, Null/Knockout)
Allele Synonym(s)	Pept1^-
Gene Symbol and Name	Slc15a1, solute carrier family 15 (oligopeptide transporter), member 1
Gene Synonym(s)
Strain of Origin	129P2/OlaHsd
Chromosome	14
Molecular Note	DNA sequence bases encoding amino acid residues 16-24 were replaced with an IRES-lacZ-neomycin selection cassette.

Tg(SLC15A1)1Dsmi

Allele Symbol: Tg(SLC15A1)1Dsmi

Allele Name	transgenic insertion 1, David E Smith
Allele Type	Transgenic (Inserted expressed sequence, Humanized sequence)
Allele Synonym(s)	huPEPT1
Gene Symbol and Name	Tg(SLC15A1)1Dsmi, transgenic insertion 1, David E Smith
Gene Synonym(s)
Site of Expression	all regions of the small intestine and specifically at the apical side of enterocytes as well as low expression in the proximal and distal segments of the colon.
Strain of Origin	B6.129P2-Slc15a1^tm1Dgen
Chromosome	UN
Molecular Note	The transgenic construct contains a human bacterial artificial chromosome (BAC) RP11-782G13 containing the human SLC15A1 (or PEPT1) gene including 5' regulatory elements, coding area, and 3' regulatory elements. The founder 1 contains one copy of the human BAC.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Research Tools
- Toxicology Research
  - drug/compound testing
  - drug metabolism

Mammalian Phenotype Terms by Genotype

References

Hu Y; Xie Y; Wang Y; Chen X; Smith DE. 2014. Development and characterization of a novel mouse line humanized for the intestinal peptide transporter PEPT1. Mol Pharm 11(10):3737-46PubMed: 25148225 MGI: J:273387

Additional - Slc15a1^tm1Dgen related

Additional - Tg(SLC15A1)1Dsmi related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Probe:Generic LacZ Probe
- Standard PCR:Tg(SLC15A1)1Dsmi
- Separated PCR:Slc15a1 Alternate1
- Genotyping resources and troubleshooting
Breeding Considerations

Mice homozygous for the targeted mutation and hemizygous for the transgene are viable and fertile. The donating investigator has not attempted to generate homozygous transgenic mice.
- Additional Breeding and Husbandry Support
Mating System
- Homozygous for Slc15a1<
- tm1Dgen>
- , Hemizygous for Tg(SLC15A1)1Dsmi x Homozygous for Slc15a1<
- tm1Dgen>
- , Noncarrier for Tg(SLC15A1)1Dsmi, or the reciprocal cross.
Citation
When using the mPepT1^-/- huPepT1 mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #65275 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

See MMRRC for Additional Conditions of Distribution

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:mPepT1-/- huPepT1

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Slc15a1tm1Dgen

Allele Symbol: Slc15a1tm1Dgen

Tg(SLC15A1)1Dsmi

Allele Symbol: Tg(SLC15A1)1Dsmi

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

References

Additional - Slc15a1tm1Dgen related

Additional - Tg(SLC15A1)1Dsmi related

Genotyping Protocols

Breeding Considerations

Mating System

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Also Known As:mPepT1^-/- huPepT1

Slc15a1^tm1Dgen

Allele Symbol: Slc15a1^tm1Dgen

Additional - Slc15a1^tm1Dgen related