ABSTRACT
Nuclear Envelope Membrane Proteins (NEMP) are a conserved family of nuclear envelope proteins that reside within the inner nuclear membrane. Even though Nemp1 knockout (KO) mice are overtly normal, they display a pronouced splenomegaly. This phenotype and recent reports describing a requirement for nuclear envelope openings during erythroblasts terminal maturation led us to examine a potential role for Nemp1 in erythropoiesis. Here, we report that Nemp1 knockout (KO) mice show peripheral blood defects, anemia in neonates, ineffective erythropoiesis, splenomegaly and stress erythropoiesis. The erythroid lineage of Nemp1 KO mice is overrepresented until the pronounced apoptosis of polychromatophilic erythroblasts. We show that NEMP1 localizes to the nuclear envelope of erythroblasts and their progenitors. Mechanistically, we discovered that NEMP1 accumulates into aggregates that localize near or close to the edge of nuclear envelope openings and Nemp1 deficiency leads to a marked decrease of both nuclear envelope openings and ensuing enucleation. Together, our results for the first time demonstrate that NEMP1 is essential for nuclear envelope openings and erythropoietic maturation in vivo and provide the first mouse model of defective erythropoiesis directly linked to the loss of an inner nuclear membrane protein of the nuclear envelope.
KEY POINTS
Nemp1 KO mice have peripheral blood defects, splenomegaly and stress erythropoiesis linked to erythroid lineage differentiation defects
NEMP1 is required for NE openings and enucleation of erythroblasts
Competing Interest Statement
The authors have declared no competing interest.