All Phenotypes Snord118<em1Jfch> MGI Mouse

premature death ( J:344970 )

• mice are born at the expected Mendelian ratio but cannot survive beyond 1 month of age

• at P20, body weight is markedly lower than in heterozygous mice and ~50% of that in wild-type mice

• at E14.5, fetal body weight is significantly lower than in wild-type controls but similar to that in heterozygous fetuses

increased neuron apoptosis ( J:344970 )

• at E12.5, brains show an aberrantly high % of p53+ cells in the cerebral cortex along with a significantly higher % of p21+/Sox2+ NPCs and Caspase-3+ cells in the VZ/SVZ regions than wild-type brains

• 2BAct treatment significantly reduces the %s of p-eIF2alpha+ cells and p53+ cells in the neocortex

decreased neuronal precursor proliferation ( J:344970 )

• at E14.5, brains show an even greater reduction in the % of BrdU+ neural progenitor cells (NPCs) and p-H3+/Pax6+ APCs in the cortex ventricular zone/subventricular zone (VZ/SVZ) regions than heterozygous brains

• 2BAct treatment significantly increases the %s of BrdU+ cells in the neocortex

abnormal brain development ( J:344970 )

• at P20, mice lack most of the neocortex, hippocampus, and corpus callosum, indicating brain growth defects

• 2BAct treatment partially rescues the brain growth and ribosomopathy defects

decreased brain weight ( J:344970 )

• at E14.5, brain weight is even lower than in heterozygous fetuses, indicating a dose-dependent effect

• at P20, brain weight is markedly lower than in heterozygous mice and ~50% of that in wild-type mice

• daily i.p. injection of 2BAct (an integrated stress response inhibitor) in pregnant mice from E11.5 to E15.5 significantly mitigates brain weight loss at E16.5

absent corpus callosum ( J:344970 )

• at P20, most of the corpus callosum is missing

absent hippocampus ( J:344970 )

• at P20, most of the hippocampus is missing

abnormal neocortex morphology ( J:344970 )

• at P20, most of the neocortex is missing

thin cerebral cortex ( J:344970 )

• at E14.5, the cerebral cortex is even thinner than in heterozygous brains

• 2BAct treatment partially rescues the reduction in cerebral cortex thickness

decreased neuronal precursor cell number ( J:344970 )

• at E14.5, brains show an even greater reduction in the % of Pax6+ apical neural progenitor cells (APCs) and Tbr2+ intermediate neural progenitor cells (IPCs) in the cerebral cortex than heterozygous brains

• neural progenitor cell (NPC) loss is due to ribosomopathy-like cellular defects, including p53 activation, cell cycle arrest, and apoptosis

• 2BAct treatment significantly increases the %s of Pax6+ APCs and Tbr2+ IPCs in the cerebral cortex

abnormal cell physiology ( J:344970 )

• an 5-ethynyl uridine (5-EU) incorporation assay showed an even greater reduction of 5-EU intensity in E12.5 cortex NPCs than in heterozygous brains, indicating a more severe defect in rRNA synthesis