Phenotypes Associated with This Genotype

Genotype
MGI:3505584

• Allelic Composition: Ascl1^tm1And/Ascl1^tm1And; Neurod4^tm1Kag/Neurod4^tm1Kag
• Genetic Background: either: (involves: 129S2/SvPas * C57BL/6 * CBA) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA)

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

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:65410 )

• double homozygous mutant embryos die between E15.5 and E17.5

vision/eye

abnormal Muller cell morphology ( J:65410 )

• retinal explant cultures from double homozygotes exhibit a significant increase in the number of Muller glia cells

• in addition, retinal explants from double homozygotes show ectopic generation of Muller cells, suggesting a fate switch from neurons to glial cells

• other cell types including rods and amacrine cells remain unaffected

absent retina bipolar cells ( J:65410 )

• after 2 weeks of culture, retinal explants derived from E15.5 double homozygotes show a complete loss of retinal bipolar cells, without significant apoptosis

nervous system

abnormal neuron differentiation ( J:65410 )

• at E10.5, double homozygotes display loss of neurons and concomitant gliogenesis in the tectum, hindbrain and retina

• at E11.5, double homozygotes show a complete absence of neurons in the midbrain, and very few neurons in the two longitudinal columns of the hindbrain

• neuronal loss occurs in the absence of abnormal proliferation or apoptosis, suggesting a fate switch from neurons to glial cells

abnormal tectum morphology ( J:65410 )

• the double mutant tectum consists of only the ventricular zone; the mantle layer is absent

• at E15.5, the ventricular cells adopt a glial fate instead of differentiating into neurons

small tectum ( J:65410 )

• in double homozygotes, the tectum is significantly thinner and devoid of neurons

abnormal Muller cell morphology ( J:65410 )

• retinal explant cultures from double homozygotes exhibit a significant increase in the number of Muller glia cells

• in addition, retinal explants from double homozygotes show ectopic generation of Muller cells, suggesting a fate switch from neurons to glial cells

• other cell types including rods and amacrine cells remain unaffected

absent retina bipolar cells ( J:65410 )

• after 2 weeks of culture, retinal explants derived from E15.5 double homozygotes show a complete loss of retinal bipolar cells, without significant apoptosis

cellular

abnormal neuron differentiation ( J:65410 )

• at E10.5, double homozygotes display loss of neurons and concomitant gliogenesis in the tectum, hindbrain and retina

• at E11.5, double homozygotes show a complete absence of neurons in the midbrain, and very few neurons in the two longitudinal columns of the hindbrain

• neuronal loss occurs in the absence of abnormal proliferation or apoptosis, suggesting a fate switch from neurons to glial cells