通過同源重組，將小鼠C3基因進(jìn)行人源化修飾。 風(fēng)險(xiǎn)提示：由于人源化C3 蛋白與小鼠補(bǔ)體調(diào)節(jié)因子的相互作用失調(diào)，hC3 小鼠會出現(xiàn)類似 C3G 患者的病理特征，純合子小鼠死亡率高（約在10周齡時(shí)出現(xiàn)死亡，至15周齡左右，死亡率達(dá)到一半），不同批次小鼠死亡率和死亡時(shí)間可能存在差異。

Fig1. Detection of C3 expression in liver by RT-PCR.?

Wild type: only one band at 359 bp with primers F1/R1(mC3);

Heterozygous: one band at 359 bp with primers F1/R1(mC3) and one band at 357 bp with primers F2/R2(hC3);?

Abbr. M, DNA marker; HO, homozygous; HE, heterozygous; WT, wild type.

Fig 2. Detection of heterozygous hC3 expression in serum by ELISA.?

Abbr. Het, heterozygous; WT, wild type.

Note: Data from the collaborator.

Fig 3. Detection of hC3 expression in serum by ELISA(n=3).

Note: The human Complement C3 ELISA Kit (ab108823) specifically recognized humanized C3.

Abbr. HO, homozygous; WT, wild type.

Fig 4. Detection of hC3 expression in eyes in HO hC3 KI mice by IF (n=5/group).

Fig 5. The HO hC3?mice showed inflammation in the portal region and bile duct hyperplasia (100× and 400×)

Fig 6. The HO hC3?mice showed glomerular sclerosis, glomerular atrophy and inflammation of the capillary tufts area (100× and 400×)

Fig 7. Body Weight of HO hC3?mouse (n=12/group).

Fig 8. Survival curve of HO hC3?mouse (n=12/group).

Fig 9. Serum Biochemistry of HO hC3?mouse (n=5/group).

Fig 10. Serum Biochemistry of HO hC3?mouse (n=5/group, a different biochemical analyzer was used than in Fig 9).

Fig 11. Urinalysis of HO hC3?mouse.

Fig 12. Single dose of ARO-C3 reduced serum hC3 levels of HO hC3 mouse (n=7-8/group).

Fig 13. Survival curve and body weight of HO hC3 mouse post ARO-C3 treatment (n=7-8/group).