| Type | disruption phenotype | Description | Embryonic lethality: embryos progress normally to the late egg cylinder stage at approximately 6.5 days post coitus (dpc), but development is arrested before 7.5 dpc (PubMed:9087432, PubMed:9501099). Mutant embryos fail to form a primitive streak and lack detectable mesoderm (PubMed:9087432). Homozygous embryos suffer from anemia as a result of abnormal fetal liver erythropoiesis (PubMed:9501099). No defect in globin gene expression are detected; abnormal red cell production being the result of a defect in the fetal liver microenvironment specific for erythroid cells (PubMed:9501099). Mice lacking both Nfe2l1 and Nfe2l2 die early between embryonic days 9 and 10 and exhibit extensive apoptosis due to marked oxidative stress in cells that is indicated by elevated intracellular reactive oxygen species levels and cell death (PubMed:12968018). Conditional knockout mice lacking Nfe2l1 in the liver do not show any liver damage when they are maintained in an unstressed condition (PubMed:15738389). In oxidative stress condition, they develop hepatic cancer following steatosis, apoptosis, necrosis, inflammation, and fibrosis (PubMed:15738389). Hepatocyte-specific deletion causes liver damage resembling the human disease non-alcoholic steatohepatitis (PubMed:18826952). Liver of conditional knockout mice lacking Nfe2l1 show massive hepatic cholesterol accumulation and damage due to inability to mediate response to cholesterol excess (PubMed:29149604). Conditional knockout mice lacking Nfe2l1 in the brain show proteasome impairment and progressive degeneration in cortical neurons (PubMed:21554501, PubMed:21536885). |
