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CRISPR-targeting of Tg(APOL1*)G1Mrpk resulted in the deleting of amino acids 388-389 generating a G2 haplotype.
These hAPOL1_G2 mice develop proteinuria and glomerulosclerosis in response to interferon-gamma.
APOL1 transgenic mice were generated using a bacterialartificial chromosome (BAC) containing a human library clone (CTD2333M18)inside a pBeloBac11 vector (BACPAC Resource Center, Children’s Hospital OaklandResearch Institute). The 100,104 bp clone contained the APOL1 gene as well as ∼25kB of upstream (including exons 1-5 of theAPOL2 gene) and ∼65kB of downstream (including exons 4-41 of the MYH9 gene) sequence. The APOL1genotype of this APOL1 BAC was determined to be G0. A G1 BAC was created usingsite-directed mutagenesis (S342G and I384M for G1; Yale O’Brien CenterTransgenic Core Facility). This G1 BAC was introduced into fertilized FVB/NJoocytes by pronuclear injection and founders were selected. As it had beenderived from a G0 BAC comprising p.E150K, the original APOL1 G1 BAC, has a Kresidue at aa position 150. To create a mouse with the same G1 coding sequencehaplotype that exists in humans, CRISPR mutagenesis was performed on the G1pronuclear stage zygotes to change the K at amino acid position 150 to E,generating the native G1 line. This mouse line was then used to generate acongenic G2 BAC transgenic line.
McCarthy GM, Blasio A, Donovan OG, Schaller LB, Bock-Hughes A, Magraner JM, Suh JH, Tattersfield CF, Stillman IE, Shah SS, Zsengeller ZK, Subramanian B, Friedman DJ, Pollak MR. Recessive, gain-of-function toxicity in an APOL1 BAC transgenic mouse model mirrors human APOL1 kidney disease. Dis Model Mech. 2021 Aug 1;14(8):dmm048952. doi: 10.1242/dmm.048952. Epub 2021 Aug 5. (Medline PMID: 34350953)
Colony Surveillance Program and Current Health Reports
Limited quantities of breeder mice (up to 2 males and 2 females or 4 mice) per investigator per month are available from a live colony, usually available to ship in under 12 weeks. Larger quantities may be available, please contact the distributing center directly at mmrrc@ucdavis.edu for more details.
Cryopreserved material may be available upon request, please inquire to mmrrc@ucdavis.edu 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.
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.