Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall C & D
*Purpose: We previously reported heterozygous c.848A > G and c.1339C > T gene mutations in the complement factor I (CFI) gene (NM_000204.3) in a kidney transplant recipient with C3 glomerulonephritis and thrombotic microangiopathy. In the present study, we characterized the relationship between the gene mutations and C3 glomerulonephritis and TMA in a mouse model.
*Methods: As contrast to the human CFI gene sequence, the CFI-D288G and CFI-P467S point mutation mice were similar and were constructed via CRISPR/Cas9 system,which was The heterozygous mouse was constructed by crossing F0 mice with C57BL/6J mouse. Disease was triggered by intraperitoneal injection of lipopolysaccharide. After 8 weeks, mice were sacrificed and urinary specimens and mice kidneys were examined.
*Results: The mice were divided into five groups: CFI-D288G heterozygous group, CFI-D288G homozygous group, CFI-P467S heterozygous group, CFI-P467S homozygous group, CFI-D288G/ P467S double heterozygous group. The wild-type group as control group. There were also separated into normal condition groups and lipopolysaccharide treatment subgroup. Proteinuria didn’t appear in all groups in normal condition. Lipopolysaccharide treatment induced significant proteinuria with the ACRs increasing in all groups. However, two CFI-D288G/P467S double heterozygous mice showed glomerular C3 deposition in mesangial area with immunofluoresce staining, which was corroborated by electron microscopy. However, there was no C3 deposition in mesangial area in other groups as control. The animal model was similar clinical and histologic evidence of C3 glomerulonephritis.
*Conclusions: This primary mouse model results showed similar clinical and histologic evidence of C3 glomerulonephritis in humans. Heterozygous gene mutations of c.848A > G and c.1339C > T in the CFI gene is potentially susceptibility gene for C3 glomerulonephritis in native kidney and allograft.
To cite this abstract in AMA style:Wen J, Song H, Ni X, Zhang M, Xu F, Zhu X. Heterozygous Gene Mutations In The Complement Factor I (cfi) Was Susceptibility Gene For The C3 Glomerulonephritis In Native Kidney And Renal Allograft [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/heterozygous-gene-mutations-in-the-complement-factor-i-cfi-was-susceptibility-gene-for-the-c3-glomerulonephritis-in-native-kidney-and-renal-allograft/. Accessed July 24, 2021.
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