Phenotypes associated with this allele
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Neurod4tm1Kag mutation
(1 available);
any
Neurod4 mutation
(24 available)
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mortality/aging
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• approximately 50% of homozygotes survive to adulthood but die within 1 year of age
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• over 40% of homozygotes die by 3 weeks of age partly because of a drinking anomaly
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behavior/neurological
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• approximately 40% of homozygotes fail to drink milk efficiently and die prior to weaning
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• homozygotes become ataxic as early as 1 week after birth
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• when placed on a rod, homozygotes fail to remain balanced for >9-10 minutes, whereas wild-type mice stay balanced for ~34 minutes
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growth/size/body
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• surviving homozygotes display a 40% reduction in body weight relative to wild-type mice
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• homozygotes exhibit a progressive growth retardation
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nervous system
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• at P7 and in adulthood, homozygotes exhibit poor lobule formation; the posterior region is more severely affected
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• in the mutant EGL, many precursor cells are TUNEL-positive, indicating cell death
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• at P7 and in adulthood, some cerebellar lobules are missing
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• at E17.5, the cerebellar anlage of homozygotes contains an EGL and appears normal
• at P7 and in adulthood, the mutant cerebellum size is reduced relative to wild-type; however, no other CNS defects are observed
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mortality/aging
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• double homozygous mutant embryos die between E15.5 and E17.5
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vision/eye
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• 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
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• after 2 weeks of culture, retinal explants derived from E15.5 double homozygotes show a complete loss of retinal bipolar cells, without significant apoptosis
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nervous system
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• 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
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• 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
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• in double homozygotes, the tectum is significantly thinner and devoid of neurons
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• 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
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• after 2 weeks of culture, retinal explants derived from E15.5 double homozygotes show a complete loss of retinal bipolar cells, without significant apoptosis
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cellular
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• 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
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Neurod4tm1Kag mutation
(1 available);
any
Neurod4 mutation
(24 available)
Neurog2tm1Fgu mutation
(0 available);
any
Neurog2 mutation
(18 available)
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mortality/aging
nervous system
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• normal number of horizontal cells
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vision/eye
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• normal number of horizontal cells
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mortality/aging
vision/eye
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• normal number of horizontal cells
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• retinal explant cultures from double homozygotes show a modest increase in the number of Muller glial cells
• in contrast, bipolar and horizontal cells are normally generated
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• retinal explant cultures from double homozygotes exhibit complete loss of amacrine cells, in the absence of significant cell death
• notably, the total number of inner nuclear layer cells and ganglion cell layer cells remains unaffected
• evidence suggests that cells that fail to differentiate into amacrine cells adopt the ganglion and Muller glial cell fates
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• decrease is not greater than that in Neurod1tm1Jle single homozygotes
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• at E17.5, optic nerves obtained from double homozygotes show a 1.7-fold increase in thickness relative to wild-type
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• in wild-type retinas, about 60% of the GCL cells are displaced amacrine cells and the others are ganglion cells; in the double-mutant retina, all of the GCL cells are ganglion cells
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• retinal explant cultures from double homozygotes show a significant increase in ganglion cells
• in addition, ectopic ganglion cells are found in the inner region of the INL of double mutant retina
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nervous system
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• retinal explant cultures from double homozygotes show a modest increase in the number of Muller glial cells
• in contrast, bipolar and horizontal cells are normally generated
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• retinal explant cultures from double homozygotes exhibit complete loss of amacrine cells, in the absence of significant cell death
• notably, the total number of inner nuclear layer cells and ganglion cell layer cells remains unaffected
• evidence suggests that cells that fail to differentiate into amacrine cells adopt the ganglion and Muller glial cell fates
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• decrease is not greater than that in Neurod1tm1Jle single homozygotes
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• retinal explant cultures from double homozygotes show a significant increase in ganglion cells
• in addition, ectopic ganglion cells are found in the inner region of the INL of double mutant retina
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• at E17.5, optic nerves obtained from double homozygotes show a 1.7-fold increase in thickness relative to wild-type
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mortality/aging
vision/eye
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• normal number of horizontal cells
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mortality/aging
nervous system
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• increase in the number of Muller cells in the inner nuclear layer
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• about 1/3 the number of photoreceptors
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• very few bipolar cells in the inner nuclear layer
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vision/eye
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• cell death was increased slightly
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• increase in the number of Muller cells in the inner nuclear layer
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• very few bipolar cells in the inner nuclear layer
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• about 1/3 the number of photoreceptors
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• very few bipolar cells, increased Muller cells
• but almost normal numbers of amacrine and horizontal
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cellular
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• cell death was increased slightly
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mortality/aging
nervous system
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• increase in the number of Muller cells in the inner nuclear layer
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• in the inner nuclear layer
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• fewer bipolar cells in the inner nuclear layer
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• fewer horizontal cells in the inner nuclear layer
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vision/eye
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• increase in the number of Muller cells in the inner nuclear layer
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• in the inner nuclear layer
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• fewer bipolar cells in the inner nuclear layer
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• fewer horizontal cells in the inner nuclear layer
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• fewer amacrine, horizontal and bipolar cells
• increase in Muller glial cells
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mortality/aging
nervous system
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• increase in the number cells and the cell bodies are scattered throughout the outer layer indicating an impairment in cell migration
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• virtually no bipolar cells
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• virtually no horizontal cells
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vision/eye
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• TUNEL+ cells are increased in the photoreceptor layer after more than 4 days in culture
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• increase in the number cells and the cell bodies are scattered throughout the outer layer indicating an impairment in cell migration
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• virtually no bipolar cells
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• virtually no horizontal cells
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• at E17.5, the retina consists of only 2 cellular layers rather than the normal 3 layers
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• fusion of the inner nuclear layer and outer nuclear layer
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• most cells are rods with some amacrine and Mueller cells also present
• Muller glial cell bodies are scattered throughout the outer layer indicating an impairment in cell migration
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• the inner boundary of the photoreceptor layer is irregular, indicating that the
arrangement of photoreceptors is disorganized
the inner boundary of the photoreceptor layer is irregular, indicating that the
arrangement of photoreceptors is disorganized
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• the inner boundary of the photoreceptor layer is irregular, indicating that the
arrangement of photoreceptors is disorganized
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cellular
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• TUNEL+ cells are increased in the photoreceptor layer after more than 4 days in culture
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Analysis Tools