Analysis Tools
mortality/aging
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• homozygotes fail to survive beyond P6
(J:48576)
• homozygotes fail to survive beyond P8
(J:97013)
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homeostasis/metabolism
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• at E10.5, E12.5, and E18.5, homozygotes show a significant reduction in the amount of glucagon expressed per cell
• by E18.5, homozygous mutant pancreata show a ~50-fold reduction in glucagon content relative to wild-type or heterozygous pancreata
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• at E18.5, homozygous mutant pancreata show a >150-fold reduction in insulin content relative to wild-type or heterozygous pancreata
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hyperglycemia
(
J:48576
)
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• by P2, homozygotes are severely hyperglycemic, exhibiting a 5-fold increase in blood glucose levels relative to wild-type littermates
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endocrine/exocrine glands
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• at death, homozygotes exhibit reduced islet mass and an aberrant, string-like islet morphology
• in contrast, exocrine cells appear morphologically unremarkable
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• at E18.5, homozygotes exhibit a large, stable pool of atypical cells that display endocrine features and express a subset of beta-cell markers but lack insulin, indicating a complete arrest of beta cell terminal differentiation
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• homozygotes display a mild reduction in the number of pancreatic polypeptide (PP)-producing cells, whereas somatostatin-producing (delta) cell numbers remain unaltered
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• as early as E10.5, homozygotes show a significant reduction in glucagon-producing cells relative to wild-type mice
• by E18.5, homozygotes contain only ~20% of wild-type alpha cell numbers
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• at E10.5, E12.5, and E18.5, homozygotes show absence of detectable insulin-positive cells in their islets
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• at E10.5, E12.5, and E18.5, homozygotes show a significant reduction in the amount of glucagon expressed per cell
• by E18.5, homozygous mutant pancreata show a ~50-fold reduction in glucagon content relative to wild-type or heterozygous pancreata
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• at E18.5, homozygous mutant pancreata show a >150-fold reduction in insulin content relative to wild-type or heterozygous pancreata
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nervous system
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• at E17.5, homozygotes exhibit retarded oligodendrocyte differentiation, with significantly reduced myelin basic protein (MBP)-positive oligodendrocytes in the ventral brain stem
• at E13.5 and E15.5, homozygotes show ventral expansion of Olig1/Olig2 expression in the spinal neuroepithelium and increased production of oligodendrocyte progenitor cells in the spinal cord
• in contrast, generation of oligodendrocyte progenitors in mutant hindbrain/midbrain (E17.5) and forebrain (P6) regions is neither delayed nor reduced
• notably, astrocytic and Schwann cell differentiation remains unaffected
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• at P4 and P8, mutant spinal cords exhibit a significantly reduced number of MBP-positive oligodendrocytes in the white matter region, and absence of MBP-positive and proteolipid protein (PLP-DM20)-positive cells in the gray matter
• at P7, mutant brains show absence of MBP-positive and PLP-DM20-positive oligodendrocytes in the corpus callosum and anterior commissure
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• at E12.5, homozygotes exhibit absence of V3 ventral neurons concomittant with a 21% increase in the number of somatic motor neurons in the spinal cord; many motor neurons are abnormally located adjacent to the floorplate
• at this stage, the dorsal boundary of somatic motor neuron generation and number of V2 neurons remains unaffected
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• homozygotes exhibit a switch from V3 ventral neuron to somatic motor neuron generation in the spinal cord
• in contrast, homozygotes show normal generation of somatic and visceral motor neurons in the hindbrain, in the absence of a ventral-to-dorsal switch
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• at E11.5 and E12.5, homozygotes exhibit reduced serotonin expression, concomittant with a virtual loss of serotonergic neurons at the r2 level of the hindbrain
• in contrast, serotonergic neurons of the dorsal raphe nuclei and dopaminergic neurons of the substantia nigra and ventral tegmental area nuclei are found in normal numbers and positions
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growth/size/body
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• at P2, homozygotes begin to exhibit severe growth retardation
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cellular
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• at E18.5, homozygotes exhibit a large, stable pool of atypical cells that display endocrine features and express a subset of beta-cell markers but lack insulin, indicating a complete arrest of beta cell terminal differentiation
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