Analysis Tools
mortality/aging
|
• mice die at or soon after birth
|
|
• mice begin to die during late embryogenesis at ~E17 and only a few are recovered at P0
|
growth/size/body
|
• at birth (P0), pups are 32% smaller than controls
|
|
• body mass is reduced at P0
|
microcephaly
(
J:271138
)
nervous system
|
• at P0, granule cell precursor (GCP) proliferation in the developing cerebellum is reduced, with 38% fewer mitotic GCPs labeled with phosphorylated histone H3 (pH3+); mitotic GCP density is reduced by 23%
• pups have only 28% more mitotic GCPs in the anterior lobe (EGL) whereas control pups have 75% more mitotic GCPs in the anterior lobe relative to the dorsal lobe, indicating impaired Shh signaling
|
|
• embryos show defects in progenitor proliferation in the developing cerebellum, cortex, and basal ganglia
• pH3+ mitotic cerebellar granule cell precursors (GCPs) are reduced by 38% at P0
• pH3+ mitotic cortical ventricular zone progenitors are reduced by 19% at E14.5
• pH3+ mitotic progenitors in the medial ganglionic eminence (MGE) and lateral ganglionic eminence (LGE) are reduced by 43% at E12.5
• however, no detectable increase in apoptosis or defects in cortical ventricular surface formation are observed and cytokinesis in ventricular cortical progenitors is normal
|
|
• widespread defects in forebrain development
|
|
• cortical plate is 13% thinner at E18.5
|
|
• widespread defects in hindbrain development
|
|
• at P0, expression of Ptch, a downstream target of Shh signaling, is reduced in the cerebellum, esp. in the Shh-responsive external granule cell layer (EGL)
|
|
• P0 brains are 14% smaller than in controls
|
|
• brain mass is reduced at E17.5
|
|
• structure of multivesicular bodies (MVBs) is disrupted in the embryonic choroid plexus
• extracellular vesicle (EV) biogenesis is impaired as the number of intraluminal vesicles (ILV) per MVB is 37% lower in choroid plexus epithelial cells than in controls and some MVBs contain abnormally large ILVs as a result of impaired ILV budding
• however, the choroid plexus ventricular surface and microvilli appear otherwise normal
|
|
• small basal ganglia
|
|
• in the ventral telencephalon, striatum area is reduced by 25% at E18.5
|
|
• cerebral cortex is smaller and thinner than in controls
• at P0, anterior-posterior (A-P) length of the cerebral cortex is shorter than in controls
|
|
• defects in cortical layers; superficial cortical layers (II-IV, Cux1+ neurons) are reduced by 25% while deep cortical layers (V-VI, Ctip2+ neurons) are reduced by 9% (less affected)
|
|
• cerebral cortex is 13% thinner at E18.5
|
|
• P0 pups have smaller olfactory bulbs than controls
|
|
• olfactory bulb is hypomorphic
|
|
• telencephalon is hypomorphic
|
|
• at P0, cerebellar Purkinje cell (PC) multivesicular bodies (MVBs) have 24% fewer intraluminal vesicles (ILVs) per MVB than controls
|
|
• smaller cerebellum with reduced foliation at P0
• however, Purkinje cell layer is intact
|
|
• cerebellar hypoplasia with a 21% reduction in perimeter at P0
|
|
• Tbr2+ intermediate progenitors are reduced by 26% at E13.5
|
cellular
|
• at P0, granule cell precursor (GCP) proliferation in the developing cerebellum is reduced, with 38% fewer mitotic GCPs labeled with phosphorylated histone H3 (pH3+); mitotic GCP density is reduced by 23%
• pups have only 28% more mitotic GCPs in the anterior lobe (EGL) whereas control pups have 75% more mitotic GCPs in the anterior lobe relative to the dorsal lobe, indicating impaired Shh signaling
|
|
• embryos show defects in progenitor proliferation in the developing cerebellum, cortex, and basal ganglia
• pH3+ mitotic cerebellar granule cell precursors (GCPs) are reduced by 38% at P0
• pH3+ mitotic cortical ventricular zone progenitors are reduced by 19% at E14.5
• pH3+ mitotic progenitors in the medial ganglionic eminence (MGE) and lateral ganglionic eminence (LGE) are reduced by 43% at E12.5
• however, no detectable increase in apoptosis or defects in cortical ventricular surface formation are observed and cytokinesis in ventricular cortical progenitors is normal
|
homeostasis/metabolism
|
• total sonic hedgehog (SHH) protein in cerebrospinal fluid (CSF) from the 4th ventricle is reduced by 38% at E14.5
• at P0, expression of Ptch, a downstream target of Shh signaling, is reduced in the cerebellum, esp. in the Shh-responsive external granule cell layer (EGL)
|
