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In contrast, active selection over prolonged periods was necessary to obtain homoplasmic NZB mtDNA mice on the same nuclear background. To further quantify the preferential germline transmission of the 129 mtDNAs, we genotyped DNA from tail tips of 864 pups and determined whether the 129-NZB mtDNA heteroplasmy changed relative to their mother. If segregation of different mtDNA types was determined by random drift alone, the mean of the frequency distribution of the progeny��s mtDNA genotypes should approximate that of their mother. However, we found that the mean distribution of the progeny��s mtDNA heteroplasmy was frequently shifted toward increased 129 mtDNA relative to their Histone Methyltransferase inhibitor mother��s (Figure?1A). Of the 864 pups genotyped, 581 (67%) had an increase in the proportion of their 129 mtDNA, whereas 244 (28%) had an increase in NZB mtDNA, and only 39 (5%) had the same mean level of 129-NZB heteroplasmy as their mothers. On average the progeny had a 5.9% (SEM?= 0.48, n?= 864) increase in the proportion of the 129 mtDNA, which was significantly greater than random (one sample t test p?DEF6 of 129 and NZB mtDNAs that remained relatively stable into adulthood (Figures 2 and S1). Moreover, the tip of the tail was easily accessible by biopsy early in the mouse��s life. The stability of the heteroplasmy of brain, heart, skeletal muscle, and tail was in marked contrast to the loss of 129 mtDNAs observed in liver and kidney or loss of NZB mtDNAs from the spleen and pancreas in adult mice (Figures PD0325901 research buy 2 and S1), a phenomenon reported for NZB-Balb/c heteroplasmic mtDNA mice (Jenuth et?al., 1997). To determine if the progressive increase in proportion of 129 mtDNA across generations was dependent on the value of maternal 129-NZB heteroplasmy level, we grouped mothers by their tail genotypes in intervals of 20% NZB mtDNAs and analyzed the average change in the percentage of heteroplasmy of the progeny in each group (Figures 1B and 1C). The progeny of mothers with 0%�C20% NZB mtDNA had on average 0.36% more of the 129 mtDNA than their mother (SEM?= 0.48, n?= 341, 95% CI 0.57%�C1.3%), progeny of mothers with 20%�C40% NZB mtDNA had an average 5.6% more 129 mtDNA (SEM?= 1.22, n?= 140, 95% CI 3.2%�C8.0%), progeny of 40%�C60% NZB mothers had 8.2% more 129 mtDNAs (SEM?= 1.78, n?= 84, 95% CI 4.7%�C11.8%), and progeny of 60%�C80% NZB mothers had 15.4% more 129 mtDNA than their mothers (SEM?= 1.32, n?= 168, 95% CI 12.8%�C18.0%). The differences in segregation between the 0%�C20% group and the 20%�C40% (p?= 0.002), 40%�C60% (p?