Analysis Tools
mortality/aging
| N |
• mice are born in normal Mendelian ratios and survive to adulthood
|
growth/size/body
|
• mice exhibit an oddly shaped head at 9 months of age
|
|
• mice show a significant reduction in body weight by P2; growth differences are maintained as mice grow older and are readily obvious by P10
• however, body weight is relatively normal at birth
|
craniofacial
|
• mice exhibit an oddly shaped head at 9 months of age
|
nervous system
|
• at E15.5, but not at E13.5, mice show a 10-fold increase in the % of cleaved caspase 3-positive (CC3+) apoptotic cells within the intermediate zone (IZ) and cortical plate (CP) relative to control and heterozygous littermates; however, the % of apoptotic cells within the ventricular zone (VZ) is unaffected
• % of CC3+ cells remains elevated as late as P2, when it becomes accompanied by a similar 10-fold increase in Iba1+ microglia cells
|
|
• cortical progenitor cells show a 10% decrease in the fraction of cells exiting the cell cycle within a 24-h period, suggesting that cell cycle length is prolonged
• however, no blocks are noted in the cell cycle with normal cell proportions in the S- and M-phase relative to control samples
|
microgliosis
(
J:334252
)
|
• at E15.5, but not at E13.5, mice exhibit more Iba1+ activated microglia within the ventricular zone (VZ) relative to control mice; however, levels of microglia within the intermediate zone (IZ) and cortical plate (CP) remain normal
• by P2, cortex shows a 10-fold increase in Iba1+ microglia cells relative to control and heterozygous samples, with a significantly higher incidence of Iba1+ CC3+ co-labeled cells
• frequency of Iba1+ cells remains significantly high at P7
|
|
• at birth (P0.5), mice show a significant reduction in brain weight resulting in a decreased brain weight to body weight ratio
|
|
• at P12, mice show a massive reduction in forebrain size relative to control and heterozygous littermates
|
|
• at P26, gross morphology of the hypoplastic forebrain is identical to that observed at P12, suggesting a developmental phenotype that does not worsen with age
|
|
• mice exhibit severe cortical hypoplasia that is present from birth
|
|
• at P2, the proportion of superficial, late-born Satb2+ neurons (upper layers IIV) is reduced by 45% with fewer Satb2+ cells present in layer V and some Satb2+ cells located below layer VI; the proportion of deep, early-born Tbr1+ neurons (layer VI) is also significantly decreased
• Ctip2 immunostaining showed both lamination and cell fate defects: the proportion of Ctip2high neurons in layer V is reduced >90%, while the proportion of Ctip2low cells shows a 60% reduction in layer VI along with a 2.7-fold increase in layers IIIII
• immunostaining of Foxp1 (normally expressed in layers IV and V of the cortex) showed an overall decrease in the proportion of Foxp1+ cells, with most located within layer IV
|
|
• at E15.5, the % of Tbr2+/Hoechst+ intermediate progenitor cells (IPCs) is slightly but significantly decreased in forebrain sections
• however, radial glia progenitor cells (RGCs) show no reduction in cell number or any blocks in cell cycle progression that alter proliferation
|
|
• neuron fate specification defects include layer VI and layer II-IV neurons that maintain Ctip2 protein expression inappropriately, a massive decrease in Ctip2+ and Foxp1+ layer V neurons, and misplaced Satb2+ neurons residing below layer VI that likely never complete their migration to the upper layers
|
immune system
microgliosis
(
J:334252
)
|
• at E15.5, but not at E13.5, mice exhibit more Iba1+ activated microglia within the ventricular zone (VZ) relative to control mice; however, levels of microglia within the intermediate zone (IZ) and cortical plate (CP) remain normal
• by P2, cortex shows a 10-fold increase in Iba1+ microglia cells relative to control and heterozygous samples, with a significantly higher incidence of Iba1+ CC3+ co-labeled cells
• frequency of Iba1+ cells remains significantly high at P7
|
cellular
|
• at E15.5, but not at E13.5, mice show a 10-fold increase in the % of cleaved caspase 3-positive (CC3+) apoptotic cells within the intermediate zone (IZ) and cortical plate (CP) relative to control and heterozygous littermates; however, the % of apoptotic cells within the ventricular zone (VZ) is unaffected
• % of CC3+ cells remains elevated as late as P2, when it becomes accompanied by a similar 10-fold increase in Iba1+ microglia cells
|
|
• cortical progenitor cells show a 10% decrease in the fraction of cells exiting the cell cycle within a 24-h period, suggesting that cell cycle length is prolonged
• however, no blocks are noted in the cell cycle with normal cell proportions in the S- and M-phase relative to control samples
|
hematopoietic system
microgliosis
(
J:334252
)
|
• at E15.5, but not at E13.5, mice exhibit more Iba1+ activated microglia within the ventricular zone (VZ) relative to control mice; however, levels of microglia within the intermediate zone (IZ) and cortical plate (CP) remain normal
• by P2, cortex shows a 10-fold increase in Iba1+ microglia cells relative to control and heterozygous samples, with a significantly higher incidence of Iba1+ CC3+ co-labeled cells
• frequency of Iba1+ cells remains significantly high at P7
|
behavior/neurological
| N |
• adult mice show no differences in home cage behavior relative to control littermates
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| neurodevelopmental disorder with dysmorphic facies and distal limb anomalies | DOID:0070514 |
OMIM:617755 |
J:334252 | |
