mortality/aging
• homozygous mutants die at birth
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endocrine/exocrine glands
• the normal peripheral distribution of non-beta hormone cells in the islets of Langerhans is disturbed
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• at E18.5, homozygotes show a 65% reduction of insulin-positive beta cells in the remaining (ventral) portion of the pancreas
• no differences are detected in the densities of the other hormone-producing cells (alpha, delta and gamma)
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• at E18.5, homozygotes display increased expression of somatostatin, an endocrine marker specific for delta cells
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• at E18.5, homozygotes display a reduction in the size of islets, most likely due to a decrease in the number of beta-cells
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• homozygotes fail to develop the dorsal lobe of the pancreas, despite the presence of an intact dorsal pancreatic mesenchyme at E9.5
• in contrast, the ventral lobe of the pancreas is found at the expected location
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• at E18.5, mutant insulin-positive islet cells display reduced expression of Glut2 and Nkx6-1, suggesting impaired beta-cell function
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growth/size/body
• at E18.5, mutant embryos are slightly smaller and display a curled body relative to wild-type embryos; however, skeletal development appears unaffected
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immune system
N |
• at E18.5, homozygotes exhibit normal early B and T lymphocyte development, despite a modest reduction in fetal liver myeloid progenitors
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