Strikingly, a cancer-associated mutation exhibited increased basal activity and failed to rescue the embryonic developmental phenotype in transgenic worms.
Notably, melanomas that have the V600E BRAF mutation exhibit increased HIF-1α expression.
In contrast, Atm knock-in heterozygous mice harbouring an in-frame deletion corresponding to the human mutation exhibit increased susceptibility to a wide variety of tumours [ 14].
Notably, cancer cells carrying mutations in BRCA1/2 exhibit increased sensitivity to topoisomerase inhibitors.
Plants containing mutations in ANT genes exhibit increased sensitivity to disruptions in polar auxin transport [ 77], suggesting that its role during embryogenesis might be related to auxins.
This approach is supported by studies of Pcsk9-knockout mice, as well as humans with missense mutations in PCSK9, which both exhibit increased sensitivity to statins [ 23, 25].
In addition, many epileptogenic mutations of SNC1A, SCN2A and SCN3A exhibit increased persistent currents (Meisler and Kearney, 2005).
Neurons from two different PSEN1 mutations (Y115C and intron 4) did not exhibit increased total or phosphorylated tau levels, compared to controls.
Mutations in components of the RNAi machinery, such as Rdp1, Ago1 and Dcr1, exhibit increased mitotic recombination frequency of rDNA repeats also in S. pombe [13].
Both male and female mice exhibit increased Aβ42∶Aβ40 ratios in aged brain, which mimics the effect of familial mutations of Presenilin-1, Presenlin-2, and the amyloid precursor protein on Aβ production.
