Phenotypes for Brpf1 Emx1 MGI:5896655 MGI Mouse

postnatal lethality, incomplete penetrance ( J:224155 , J:241490 )

• most pups die prior to weaning at P21 (J:224155)

• most mice die before weaning (J:241490)

• however, a minority of mice survive beyond weaning (J:241490)

prenatal lethality, incomplete penetrance ( J:241490 )

• slightly fewer than mice are born

N	• mice exhibit normal cerebellum

abnormal radial glial cell morphology ( J:224155 )

• distribution of Gfap+ radial glial cells in the dentate gyrus is slightly disturbed at E16.5 but becomes moderately and completely disorganized at P0 and P10, respectively

decreased radial glial cell number ( J:224155 )

• significantly fewer Gfap+ radial glial cells are found in the granular cell layer of the dentate gyrus at P10

abnormal neuronal precursor cell migration ( J:224155 )

• at P10, Tbr2+ intermediate neuronal progenitors fail to translocate to the subgranular zone and the hilum of the dentate gyrus, with some of Tbr2+ progenitors remaining at the outer rim of the molecular cell layer

• only a few NeuroD1+ neuroblasts are present in the granular cell of the dentate gyrus at P10, and almost none is found in the subgranular zone at P24, indicating abnormal migration of NeuroD1+ neuroblasts

• cell cycle progression of the dentate migration stream is impaired at E15.5, most likely through the G1 phase

decreased neuronal precursor proliferation ( J:224155 , J:241490 )

• at P10 and P24, Ki67+ neuronal precursors are missing in the dentate gyrus, indicating a dramatic lack of proliferation in the subgranular zone (J:224155)

• at E15.5, the number of BrdU+ progenitors is normal in the dentate migration stream whereas the Ki67+ cycling cell population (at G1, S, G2 and M, but not G0) is significantly increased, thereby decreasing the ratio of S-phase (BrdU+) over proliferating (Ki67+) cells (J:224155)

thin cortical plate ( J:241490 )

• at E15.5

• thinner layers V to VI at P0

• immediately after birth

abnormal corpus callosum morphology ( J:224155 )

decreased corpus callosum size ( J:241490 )

• absence of ventral and dorsal but not middle transverse sections at P14 and P24, but not E17.5 with only caudal reduction at P0

abnormal hippocampus morphology ( J:224155 )

• at P19, the hippocampus exhibits abnormal axon and dendritic trees in the dentate gyrus as well as in the CA regions

• at P10, the hippocampus fissure is malformed

abnormal hippocampus development ( J:224155 )

• mice exhibit partial agenesis of the hippocampus

abnormal dentate gyrus morphology ( J:224155 )

• at P0, the suprapyramidal blade is underdeveloped, with one end remaining attached to the ventricular zone, whereas the infrapyramidal blade is missing in the developing dentate gyrus

• at P0, a much smaller population of Ctip2+ neurons is observed in the suprapyramidal blade

• at P19, fewer neurons are observed in the dentate gyrus

decreased dentate gyrus size ( J:224155 )

• mice exhibit dentate gyrus hypoplasia at E17.5 and P0

abnormal hippocampal mossy fiber morphology ( J:224155 )

• at P8, mossy fibers of the suprapyramidal bundles and dentate hilum are missing

abnormal hippocampus pyramidal cell layer ( J:224155 )

• at P10 and P24, the pyramidal layers of CA1 and CA3 are not as tightly packed as in control mice

abnormal hippocampus neuron morphology ( J:224155 )

• at P19, the hippocampus exhibits disorganized neurons with less robust dendritic trees

• at P24, FoxG1+ neurons are abnormally found in the CA3 field and are not as tightly packed in the CA1 field

abnormal hippocampus region morphology ( J:224155 )

• nuclear layers of CA1 and CA3 appear more diffusely packed than in control mice

abnormal hippocampus CA1 region morphology ( J:224155 )

• border between cornu ammonis 1 (CA1) and the subiculum is not clearly defined at P10 or P24

increased subiculum size ( J:224155 )

• subiculum is expanded at P10 and P24

abnormal neocortex morphology ( J:224155 , J:241490 )

• altered lamination observed as early as E14.5 (J:241490)

decreased neocortex size ( J:241490 )

• shorter rostral-caudal length and thinner than in control mice

abnormal neuronal stem cell morphology ( J:224155 )

• at P0, the population of Sox2+ neural stem cells is decreased in the dentate gyrus; no enrichment of Sox2+ neural stem cells is noted in the subgranular zone at P10 and P14, unlike in control mice

decreased neuronal precursor cell number ( J:224155 )

• fewer Dcx+ immature neurons are found in the subgranular zone of the dentate gyrus at P10 and P24

• only a few NeuroD1+ neuroblasts are present in the granular cell of the dentate gyrus at P10, and almost none is found in the subgranular zone at P24

abnormal behavior ( J:241490 )

• one surviving mouse exhibited impaired marble burying behavior

decreased food intake ( J:241490 )

limb grasping ( J:241490 )

abnormal nest building behavior ( J:241490 )

• impaired nest building

decreased body size ( J:241490 )

• at P10, but not P5, and persisting beyond weaning

prenatal growth retardation ( J:241490 )

abnormal cell physiology ( J:240552 )

• reduced histone H3K23 acetylation in cortex extracts

abnormal cell cycle checkpoint function ( J:224155 )

• cell cycle progression of the dentate migration stream is impaired at E15.5, most likely through the G1 phase; defects at E15.5 are smaller than those at or after P10

• M phase of the cell cycle appears unaffected