Strain Name:
B6.Cg-Slc15a1tm1Dgen Tg(SLC15A1)1Dsmi/Mmjax
Stock Number:
065275-JAX
Citation ID:
RRID:MMRRC_065275-JAX
Other Names:
huPepT1

Gene Information

Slc15a1tm1Dgen
Name: solute carrier family 15 (oligopeptide transporter), member 1; targeted mutation 1, Deltagen
Synonyms: Pept1-
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 14
Alteration at locus: Knockout
Slc15a1
Name: solute carrier family 15 (oligopeptide transporter), member 1
Synonyms: PEPT1, PECT1
Type: Gene
Species: Mus musculus (mouse)
Chromosome: 14
Alteration at locus: Knockout
NCBI: 56643
VEGA: 14
Homologene: 38006
Tg(SLC15A1)1Dsmi
Name: transgenic insertion 1, David E Smith
Synonyms: huPEPT1
Type: Allele
Species: Homo sapiens (human)
Chromosome: unknown
Alteration at locus: Transgenic (random, gene disruption)
SLC15A1
Name: solute carrier family 15 member 1
Type: Gene
Species: Homo sapiens (human)
Chromosome: 13
Alteration at locus: Transgenic (random, gene disruption)
Genetic Alterations
The peptide transporter 1 (PepT1), also known as solute carrier family 15 member 1 (SLC15A1), is a protein that, in humans, is encoded by SLC15A1 gene, which mediates the cellular uptake of di-/tripeptides in addition to several peptidomimetic drugs. In this line, DNA sequence bases encoding amino acid residues 16-24 were replaced with an IRES-lacZ-neomycin selection cassette. The transgenic construct stems from 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. Founder #1 presented with one copy of the human BAC.
Phenotype
The proton-coupled oligopeptide transporter PEPT1 (SLC15A1) is abundantly expressed in the small intestine, and found to mediate the uptake of di/tripeptides and peptide-like drugs from the intestinal lumen. The humanized huPePT1 mouse strain has no obvious behavioral or pathological phenotype. The mRNA and protein profiles indicated that huPEPT1 mice had substantial PEPT1 expression in all regions of the small intestine (i.e., duodenum, jejunum, and ileum) along with low but measurable expression in both, proximal and distal segments of the colon. These findings suggest that huPepT1 mice may provide a valuable tool in the drug discovery process by better predicting the oral pharmacokinetic profiles of PepT1 substrates in humans.
Mammalian Phenotype Terms
Allelic Composition: (Genetic Background: )

  • digestive/alimentary system
MeSH Terms
  • Animals
  • Female
  • Humans
  • Intestinal Mucosa/metabolism
  • Intestine, Small/metabolism
  • Male
  • Mice
  • Mice, Knockout
  • Mice, Mutant Strains
  • Models, Animal
  • Peptide Transporter 1
  • Symporters/genetics
  • Symporters/metabolism
  • Anti-Bacterial Agents/administration & dosage
  • Anti-Bacterial Agents/blood
  • Anti-Bacterial Agents/metabolism
  • Anti-Bacterial Agents/pharmacokinetics
  • Cefadroxil/administration & dosage
  • Cefadroxil/blood
  • Cefadroxil/metabolism
  • Cefadroxil/pharmacokinetics
  • Colon/metabolism
  • Crosses, Genetic
  • Dose-Response Relationship, Drug
  • Half-Life
  • In Vitro Techniques
  • Intestinal Absorption
  • Jejunum/metabolism
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Perfusion
  • Species Specificity
  • Tissue Distribution
Strain Development
In brief, bacterial artificial chromosomes (BACs) containing the PEPT1 gene (SLC15A1 - NCBI Gene:6564) were obtained from a human BAC library (Empire Genomics, Buffalo, NY). A BAC clone [RP11-782G13; ∼179 kb; CHR13 (98,091,462–98,270,723)], containing the entire 5′-terminal regulatory elements, coding area, and 3′-terminal regulatory elements, was then microinjected into the male pronucleus of fertilized one-cell embryos obtained from Pept1–/– mice on a C57BL/6 background. The pronuclear stage embryos were then transferred into the uterus of pseudopregnant recipient animals. Founder mice were screened to identify an animal containing one copy of the human BAC after which these animals were bred (i.e., mPept1–/–/hPEPT1+/– × mPept1–/–/hPEPT1–/– mice) to maintain hemizygous transgenic lines.
Suggested Control Mice
C57BL/6J
Donor
David Smith, Ph.D., UMICH College of Pharmacy.
Yongjun Hu, Ph.D., University of Michigan - Ann Arbor.
Primary Reference

Hu Y, Xie Y, Wang Y, Chen X, Smith DE. Development and characterization of anovel mouse line humanized for the intestinal peptide transporter PEPT1. MolPharm. 2014 Oct 6;11(10):3737-46. doi: 10.1021/mp500497p. Epub 2014 Sep 2. PubMedPMID: 25148225; PubMed Central (Medline PMCID: PMC4186676)

Hu Y, Smith DE. In Silico Prediction of the Absorption and Disposition ofCefadroxil in Humans using an Intestinal Permeability Method Scaled fromHumanized PepT1 Mice. Drug Metab Dispos. 2019 Mar;47(3):173-183. doi:10.1124/dmd.118.084236. Epub 2018 Dec 28. (Medline PMID: 30593545)

Hu Y, Smith DE. Species differences in the pharmacokinetics of cefadroxil asdetermined in wildtype and humanized PepT1 mice. Biochem Pharmacol. 2016 May1;107:81-90. doi: 10.1016/j.bcp.2016.03.008. Epub 2016 Mar 12. (Medline PMID: 26979860)

Epling D, Hu Y, Smith DE. Evaluating the intestinal and oral absorption of theprodrug valacyclovir in wildtype and huPepT1 transgenic mice. Biochem Pharmacol. 2018 Sep;155:1-7. doi: 10.1016/j.bcp.2018.06.010. Epub 2018 Jun 21. (Medline PMID: 29935147)

Colony and Husbandry Information

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email csmmrrc@jax.org .
Coat Color
Black
Eye
Black
MMRRC Breeding System
Backcross and random intra-strain mating
Generation

N8 (C57BL/6NCrl), F10

Overall Breeding Performance
Excellent
NOTE: "Hemizygote" as used here refers to males carrying a mutation on the X Chromosome or mice of either sex carrying an inserted transgene with no homologous allele on the other chromosome.
Viability and Fertility: Female Male Comments
Homozygotes are viable: Undetermined Undetermined
Homozygotes are fertile: Undetermined Undetermined
Hetero/Hemizygotes are fertile: Yes Yes
Age Reproductive Decline: Greater than 12 months Greater than 12 months
Average litter size
10-14
Recommended wean age
3 Weeks
Average Pups Weaned
10-14

Order Request Information

Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org for more information.

Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

The donor or their institution limits the distribution to non-profit institutions only.

Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # Description Distribution Fee / Unit (US $) Units Notes
065275-JAX-M03-F
065275-JAX-M03-M
065275-JAX-M04-F
065275-JAX-M04-M
Homozygous for Slc15a1<tm1Dgen>/Hemizygous for Tg(SLC15A1)1Dsmi
Homozygous for Slc15a1<tm1Dgen>/ Hemizygous for Tg(SLC15A1)1Dsmi
Homozygous for Slc15a1<tm1Dgen>/ Noncarrier for Tg(SLC15A1)1Dsmi
Homozygous for Slc15a1<tm1Dgen>/ Noncarrier for Tg(SLC15A1)1Dsmi
$218.00 / Non-Profit Per Mouse The csmmrrc@jax.org may assess additional fees for any special requests (e.g., specific age or weight of mice, etc.).
065275-JAX-SPERM Cryo-preserved spermatozoa $437.00 / Non-Profit Aliquot Approximate quantity3
065275-JAX-RESUS Litter recovered from cryo-archive $2,022.00 / Non-Profit Litter Recovered litter4; additional fees for any special requests.
Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org for more information.

1 The distribution fee covers the expense of rederiving mice from a live mouse; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

2 An aliquot contains a sufficient number of embryos (in one or more vials or straws and based on the transfer success rate of the MMRRC facility) to transfer into one to three recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

3 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.

4 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.