Kif18a mutant mice display similarly elevated levels of micronuclei in healthy tissues, regardless of p53 status. (A) Schematic of cross to generate Kif18agcd2, Trp53tm1 Tyj mice. (B) Quantification of micronucleated cells, as observed by Hoechst stain, in thymus, spleen, and liver tissues from healthy individuals homozygous for the Kif18Agcd2 mutation and with WT Trp53, Trp53tm1 Tyj/+, or Trp53tm1 Tyj/tm1 Tyj. n = 3 tissue types from one biological sample per each genotype. Percentages are the average from two independent counts of each tissue. Micronucleated cell counts were Kif18agcd2/gcd2, Trp53+/+, 83 of 1,317 in thymus, 119 of 2,587 in spleen, and 57 of 1,115 in liver; Kif18agcd2/gcd2, Trp53+/tm1 Tyj, 120 of 1,496 in thymus, 68 of 1,468 in spleen, and 41 of 735 in liver; and Kif18agcd2/gcd2, Trp53tm1 Tyj/tm1 Tyj, 36 of 602 in thymus, 97 of 2,410 in spleen, and 46 of 811 in liver (Table S1). (C) Representative images of micronuclei (yellow arrowheads) observed in healthy (left to right) thymus, spleen, and liver tissue sections from a Kif18agcd2/gcd2, p53+/+ mouse. (D) Plot showing percentages of micronucleated Ret (of total Ret) quantified via peripheral blood assay from male and female mice of genotypes Kif18agcd2/gcd2, Trp53tm1 Tyj/tm1Tyj (n = 8); Kif18agcd2/gcd2, Trp53+/+ (n = 8); Kif18agcd2/+, Trp53tm1 Tyj/tm1Tyj (n = 8); and Kif18a+/+, Trp53tm1 Tyj/tm1Tyj and Trp53+/+ (n = 8). Data points indicate individual biological replicates. Error bars represent SD. Statistical analysis was performed using pairwise ANOVA comparisons of means, α = 0.05. *, P < 0.01.
