Phenotypes Associated with This Genotype

Genotype
MGI:3698831

• Allelic Composition: Ddb1^tm1Spg/Ddb1^tm1Spg; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * SJL

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

neonatal lethality, complete penetrance ( J:117820 )

• newborn mice die within 24 hours

nervous system

abnormal cerebellum external granule cell layer morphology ( J:117820 )

• EGL of cerebellum (proliferative zone) is almost absent in mutants

decreased brain size ( J:117820 )

• overall size of mutant brains is decreased at birth compared to wild-type

abnormal fourth ventricle morphology ( J:117820 )

• the fourth (IV) ventricle is open to the brain surface and filled with blood

abnormal lateral ventricle morphology ( J:117820 )

• nearly complete loss of cells in the ventricular (VZ) and subventricular zones (SVZ) of lateral ventricles

enlarged lateral ventricles ( J:117820 )

• lateral ventricles are dramatically enlarged

abnormal cerebral aqueduct morphology ( J:117820 )

• the aqueduct of Sylvius is open to the brain surface and filled with blood

abnormal cerebral cortex morphology ( J:117820 )

• remaining laminated layers show reduced cellularity and numerous red blood cells

thin cerebral cortex ( J:117820 )

• cortex is much thinner at E16.5 from excess cell death

abnormal olfactory bulb morphology ( J:117820 )

• VZ and SVZ of olfactory bulb are missing

small cerebellum ( J:117820 )

• much smaller than controls

abnormal nervous system physiology ( J:117820 )

• most dorsolateral cortical regions lack any vasculature; remaining vessels are dilated compared to control

• many blood vessels in cerebellum are dilated, but severe hemorrhage is only detected in rostrolateral tip

intracranial hemorrhage ( J:117820 )

• bleeding is restricted to the forebrain mainly

cerebellum hemorrhage ( J:117820 )

• newborn mutants all exhibit severe hemorrhage within cerebral hemispheres and cerebellum

intracerebral hemorrhage ( J:117820 )

• newborn mutants all exhibit severe hemorrhage within cerebral hemispheres and cerebellum

abnormal neuron apoptosis ( J:117820 )

• at E14.5, neuroprogenitor cells (NPC) show massive apoptotic death in SVZ and VZ, including pyknotic cells in ganglionic eminence; peak is at E15.5

• at E16.5, cavitations result from hypocellularity in VZ and SVZ

vision/eye

increased lens epithelium apoptosis ( J:117820 )

• at E15.5, many progenitor epithelial cells are apoptotic

• at E16.5. fewer epithelial cells are present in central pool or equatorial region, with pyknotic nuclei found in whole epithelium layer

abnormal lens morphology ( J:117820 )

• lenses are severely degenerated in newborn mutants

• lens has fewer cells; cells are abnormally shaped and disorganized

cataract ( J:117820 )

• lens is much less transparent than in controls

cardiovascular system

abnormal blood vessel morphology ( J:117820 )

• cerebrovascular vessels are abnormally dilated and many rupture

• in newborn brains, there are ~12-fold fewer vessels compared to controls

intracranial hemorrhage ( J:117820 )

• bleeding is restricted to the forebrain mainly

cerebellum hemorrhage ( J:117820 )

• newborn mutants all exhibit severe hemorrhage within cerebral hemispheres and cerebellum

intracerebral hemorrhage ( J:117820 )

• newborn mutants all exhibit severe hemorrhage within cerebral hemispheres and cerebellum

cellular

increased lens epithelium apoptosis ( J:117820 )

• at E15.5, many progenitor epithelial cells are apoptotic

• at E16.5. fewer epithelial cells are present in central pool or equatorial region, with pyknotic nuclei found in whole epithelium layer

abnormal neuron apoptosis ( J:117820 )

• at E14.5, neuroprogenitor cells (NPC) show massive apoptotic death in SVZ and VZ, including pyknotic cells in ganglionic eminence; peak is at E15.5

• at E16.5, cavitations result from hypocellularity in VZ and SVZ