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. 2020 Apr;30(4):540–552. doi: 10.1101/gr.258400.119

Figure 4.

Figure 4.

Combinatorial effects of multiple mutations on health and longevity. (A) Multiple lines (895, 520, 4654, 4751, 4799, J_57L, and M_199L) carry lesions in more than one gene that either independently or additively improve health. Kdm4a and Cd22 in line 520, Tm7sf2 and Gtf3c5 in line 4654, and Arhgef15 and Spin1 in line 4751 show independent effects on health, whereas the other mutations show positive combinatorial effects on Mecp2/Y health. (B) Mecp2/Y mice from line 895, carrying mutations in Sqle and/or Rbbp8, show increased longevity when both mutations are present (Mecp2/Y;Rbbp8+/−;Sqle+/−; n = 7, median survival 277 d) when compared to Mecp2/Y mice carrying either mutation alone (Mecp2/Y;Rbbp8+/−;Sqle+/+; n = 35, median survival 112 d or Mecp2/Y;Rbbp8+/+;Sqle+/−; n = 47, median survival 88 d). For Mecp2/Y;Rbbp8+/+;Sqle+/+; n = 94, the median survival was 77 d. (P < 0.0001 by Mantel-Cox test, for each comparison of Mecp2/Y;Rbbp8+/+;Sqle+/+ to any of the three groups). These data include the founder 895, N3 animals (genotyped for both Rbbp8 and Sqle) and all of the N5 animals generated.