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.
David E. Smith, University of Michigan
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Reporter, Null/Knockout) | Slc15a1 | solute carrier family 15 (oligopeptide transporter), member 1 |
Allele Type |
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Transgenic (Inserted expressed sequence, Humanized sequence) |
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.
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 Slc15a1tm1Dgen on the C57BL/6NCrl congenic background (B6N.129P2-Slc15a1tm1Dgen). Founder mice were bred to C57BL/6 inbred mice. The donating investigator indicates that the founder contains one copy of the human BAC.
The Slc15a1tm1Dgen 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).
Allele Name | targeted mutation 1, Deltagen |
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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. |
Allele Name | transgenic insertion 1, David E Smith |
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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) | |
Strain of Origin | B6.129P2-Slc15a1tm1Dgen |
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. |
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.
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.
Facility Barrier Level Descriptions
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.
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