Table 1.
Pregnancy outcomes of ESC chimeric embryos carrying mtDNA mutations.
| Cell line (sex) | Pathogenic mutations (heteroplasmy %) | Type of negative selection for mutations | No. of ET | No. of implantation (%/ET) | No. of total term pups (%/ET) | No. of live pups (%/ET) | No. of chimeras | No. of high chimerism chimerasb (sex) |
|---|---|---|---|---|---|---|---|---|
| ND6-100 (female) | 6106A > T COXI (94%) 13026 T > C ND5 (95%) 13967C > T ND6 (100%) | High heteroplasmy | 533 | 195 (36.6%) | 90 (16.9%) | 76 (14.3%) | 35 | 4 (female) |
| ND2-50 (female) | 4871A > T ND2 (50%) | High heteroplasmy | 588 | 227 (38.6%) | 74 (12.6%) | 64 (10.9%) | 34 | 2 (female) 1 (male) |
| ATP8-62 (male) | 7769C > G ATP8 (62%) | High heteroplasmy | 394 | 139 (35.3%) | 47 (11.9%) | 39 (9.9%) | 25 | 7 (male) |
| COXIII-81 (female) | 6726A > G COXI (63%) 9138G > A/9278A > T COXIII (81%/81%) 12853C > T/13441C > T ND5 (52%/91%) | Selected gene with high heteroplasmy | 278 | 93 (33.5%) | 23 (8.3%)a | 19 (6.8%)a | 12 | 1 (male) |
| Control-1 (female) | None | None | 239 | 92 (38.4%) | 40 (16.7%)a | 35 (14.6%)a | 17 | 3 (female) 1 (male) |
aThe rate of term pups in COXIII-81 chimeras was significantly lower than that in control-1 chimeras (P < 0.01).
bHigh chimerism chimera was defined as ≥50% chimerisms determined by coat colors and whole mtDNA sequencing for C4891T SNP between B6N ESC (C) and host ICR (T).