• Background: APOL1 encodes a lipid-binding protein that functions in innate immune defense and maintains cellular homeostasis. APOL1 is primarily expressed in kidney podocytes, endothelial cells, and various other cell types including hepatocytes. Genetic variants of APOL1 are strongly linked to an increased risk of chronic kidney disease and focal segmental glomerulosclerosis.
• Gene editing strategy: The full coding sequences of human APOL1 gene (variant G1 alleles), including the promoter, 5’UTR and 3’UTR regions are inserted into mouse Hipp11 (H11) locus in B-hAPOL1-G1 mice.
• Validation: Human APOL1-G1 mRNA was exclusively detectable in homozygous B-hAPOL1-G1 mice. Human APOL1 protein was exclusively detectable in homozygous B-hAPOL1-G1 mice but not in wild-type C57BL/6JNifdc mice.
• Application: This product is used for pharmacodynamics and safety evaluation of kidney disease such as focal segmental glomerulosclerosis (FSGS)

Gene targeting strategy for B-hAPOL1-G1 mice. The full coding sequences of human APOL1 gene (variant G1 alleles), including the promoter, 5’UTR and 3’UTR regions are inserted into mouse Hipp11 (H11) locus in B-hAPOL1-G1 mice.

Strain specific analysis of APOL1-G1 mRNA expression in wild-type C57BL/6JNifdc and B-hAPOL1-G1 mice by RT-PCR. Kidney RNA were isolated from wild-type C57BL/6JNifdc (+/+) and homozygous B-hAPOL1-G1 mice (H/H), then cDNA libraries were synthesized by reverse transcription, followed by PCR with human APOL1-G1 primers. Human APOL1-G1 mRNA was exclusively detectable in homozygous B-hAPOL1-G1 mice.

Strain specific analysis of APOL1-G1 gene expression in wild-type C57BL/6JNifdc mice and B-hAPOL1-G1 mice by RT-qPCR. Kidney RNA were isolated from wild-type C57BL/6JNifdc mice (+/+) (female and male, 7 week-old, n=3) and homozygous B-hAPOL1-G1 mice (H/H) (female and male, 7 week-old, n=3). Values are expressed as mean ± SEM. ND: Not Detectable.

Strain specific hAPOL1 expression analysis in wild-type C57BL/6JNifdc mice and homozygous B-hAPOL1-G1 mice by ELISA. Serum was collected from wild-type C57BL/6JNifdc mice (+/+) (male, n=3, 8-week-old) and homozygous B-hAPOL1-G1 mice (H/H) (male, n=3, 8-week-old). Expression level of human APOL1 were analyzed by ELISA (human APOL1 ELISA kit:Proteintech, KE00047). Human APOL1 was exclusively detectable in homozygous B-hAPOL1-G1 mice. Values are expressed as mean ± SEM.