B6(Cg)-Abcc1tm1.1(ABCC1)Pahnk/Kctt

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EMMA IDEM:16165
Citation informationRRID:IMSR_EM:16165 

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International strain nameB6(Cg)-Abcc1tm1.1(ABCC1)Pahnk/Kctt
Alternative nameB6(Cg)-Abcc1(tm1.1(ABCC1)Pahnk)/Pahnk
Strain typeTargeted Mutant Strains : Knock-in
Allele/Transgene symbolAbcc1tm1.1(ABCC1)Pahnk
Gene/Transgene symbolAbcc1

Information from provider

ProviderJens Pahnke
Provider affiliationDepartment of Pathology, Pahnke Lab (www.pahnkelab.eu)
Genetic informationAbcc1 humanized floxed knock-in model. The murine exon 2 of the Abcc1 gene locus has been replaced in‑frame with the human ABCC1 coding sequence, yielding a chimeric protein that is >99.9 % human (only a single amino‑acid difference remains). The native mouse promoter and first exon are preserved to maintain physiological regulation. The human cassette is flanked by loxP sites, allowing cre recombinase‑mediated deletion of the coding sequence (hABCC1-/-). Two point mutations in exon 3 introduce stop codons in all three reading frames to prevent translation of any residual transcript after recombination. A neomycin‑resistance cassette flanked by flippase‑recognition target (FRT) sequences was introduced into the targeting vector to enable positive selection of clones, and flp‑mediated excision was achieved by crossing the founders with C57BL/6J flp‑deleter mice.
Phenotypic informationHomozygous:
Mice homozygous for the humanized hABCC1 allele (hABCC1-flx/flx) appear phenotypically normal with respect to appearance, growth, fertility, coat condition, and overall health, and are indistinguishable from wild-type C57BL/6J controls. At the molecular level, they express human ABCC1 mRNA (lower than endogenous mouse Abcc1 in brain but higher in lung) and ABCC1 protein at levels comparable to those of wild-type mice, with approximately 60% higher expression in the brain. Functional PET imaging with 6-bromo-7-[¹¹C]methylpurine shows tracer clearance from brain and lung with kinetics similar to wild-type animals, with approximately 43% faster elimination from the brain, indicating that the human transporter is functional and replaces the murine protein. Transport remains sensitive to MK571, which increases tracer retention in both humanized and wild-type mice.

Heterozygous:
Heterozygous (hABCC1-flx/+) mice have not been formally evaluated, but no phenotypic or functional changes are expected.
Breeding historyRecipient blastocysts were harvested from B6(Cg)-Tyrc-2J/J mice. After microinjection, four C57BL/6N ES cell clones were selected for reimplantation into pseudopregnant OF1 females; 6 male chimeras derived from 3 distinct clones were generated, exhibiting
References
  • Generation and Characterization of an Abcc1 Humanized Mouse Model (hABCC1flx/flx ) with Knockout Capability.;Krohn Markus, Zoufal Viktoria, Mairinger Severin, Wanek Thomas, Paarmann Kristin, Brüning Thomas, Eiriz Ivan, Brackhan Mirjam, Langer Oliver, Pahnke Jens, ;2019;Molecular pharmacology;96;138-147; 31189668
Homozygous fertileyes
Homozygous viableyes
Homozygous matings requiredno
Immunocompromisedno

Information from EMMA

Archiving centreKarolinska Institutet, Stockholm, Sweden
Animals used for archivingheterozygous C57BL/6J females

Literature references

  • Generation and Characterization of an Abcc1 Humanized Mouse Model (hABCC1flx/flx ) with Knockout Capability.;Krohn Markus, Zoufal Viktoria, Mairinger Severin, Wanek Thomas, Paarmann Kristin, Brüning Thomas, Eiriz Ivan, Brackhan Mirjam, Langer Oliver, Pahnke Jens, ;2019;Molecular pharmacology;96;138-147; 31189668

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Requesting frozen sperm or embryos is generally advisable wherever possible, in order to minimise the shipment of live mice.

  • Frozen sperm. Delivered in 4 weeks (after paperwork in place). €1740*
  • Rederivation of mice from frozen stock, delivery time available upon request . €3880*

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