Thus, we rather interpret the PE reduction in psd1Δ and psd2Δ as a predominant consequence of their primary loss of enzymatic function and not as a result of the dead cell population.
Primary candidates for loss-of-function studies can be chosen by identifying kinase genes with dominant expression and then comparing them with closely linked family members.
Indeed, even severe primary mitochondrial diseases caused by loss-of-function nuclear or mitochondrial DNA mutations affecting mitochondrial electron transport chain complexes exhibit variable cardiac involvement (Holmgren et al, 2003).
Here, we report plasma lipidomic profiling results for a cohort of patients with severe IR due to either congenital lipodystrophy (LD), a state characterized by primary adipose tissue dysfunction, or loss-of-function mutations in the genes encoding the insulin receptor signalling pathway, sometimes referred to as 'insulin receptoropathies' (INSR).
To date, the clinical management of CF focuses on treating CF symptoms, yet fails to address the primary cause of CF, namely the loss-of-function of CFTR.
The discordant results reported here between the effects of miR-16 overexpression in an orthotopic transplant model in immunocompromised mice and miR-16 deletion in a primary tumor model in immunocompetent mice demonstrate the importance of utilizing complementary gain-of-function and loss-of-function approaches and primary tumor model systems for the study of metastasis.
Primary Drosophila neurons carrying well characterised ena loss-of-function mutant alleles (enaGC1, ena23) displayed severely reduced filopodia numbers (46 69%; Fig. 1F, I), as was similarly reported for epithelial cells at the leading edge during dorsal closure in Drosophila embryos [21], [22].
To further test the functional significance of miR-16 as a metastasis suppressor gene, we used a loss-of-function approach in primary sarcomas.
Hence, using the described experimental setup, i.e. activation of T cells and nucleofection, RNAi allows specific loss-of-function studies in primary murine T cells in vitro.
Overexpression and loss-of-function experiments in primary cell culture (19, 112) and in chick embryos (137) indicate that SOX10 prevents precursors from differentiating into neurons.
