mortality/aging
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• fewer pups are born than expected
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endocrine/exocrine glands
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• mammary gland development often outpaces that of controls during puberty, however by 9-10 weeks of age, development of the ductal tree is similar to controls
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• during pregnancy, mammary lobuloalveoli fail to differentiate correctly
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• inguinal mammary glands of mutant mothers 1 day postpartum show abnormal alveolar organization; alveolar epithelial cells do not form a coherent boundary and are not columnar, lipid globules fill most of the lumens and are also trapped inside epithelial cells
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• exhibit defective lactation and expression of major milk genes is 20-30% lower at day 1 of lactation
• offspring of mutant mothers, irregardless of genotype, show perinatal lethality, with 82% of pups becoming emaciated and dying between birth and P10; pups survive when fostered with controls
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nervous system
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N |
• myelin sheaths in the brain are of normal thickness
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• cerebellum exhibits increased numbers of large interneurons in the granule cell layer, however neuromuscular junctions develop normally
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• at E17.5, ectopic nerve projections persist and result in an ectopic cranial nerve between the geniculate and trigeminal ganglia
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reproductive system
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• during pregnancy, mammary lobuloalveoli fail to differentiate correctly
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cardiovascular system
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N |
• exhibit rescue of the cardiac defects observed in homozygous Erbb4 mutants
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craniofacial
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N |
• observe no obvious defects in cranial skeleton or inner ear, lower jaw or tooth development
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embryo
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• exhibit aberrant migration of a subpopulation of rhombomere 4 (r4) neural crest cells into r3-adjacent cranial mesenchyme
• by E11, show aberrantly projecting axons extending through r3-adjacent mesenchyme, connecting the geniculate/cochleovestibular ganglion complex with the trigeminal ganglion
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integument
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• mammary gland development often outpaces that of controls during puberty, however by 9-10 weeks of age, development of the ductal tree is similar to controls
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|
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• during pregnancy, mammary lobuloalveoli fail to differentiate correctly
|
|
|
• inguinal mammary glands of mutant mothers 1 day postpartum show abnormal alveolar organization; alveolar epithelial cells do not form a coherent boundary and are not columnar, lipid globules fill most of the lumens and are also trapped inside epithelial cells
|
|
|
• exhibit defective lactation and expression of major milk genes is 20-30% lower at day 1 of lactation
• offspring of mutant mothers, irregardless of genotype, show perinatal lethality, with 82% of pups becoming emaciated and dying between birth and P10; pups survive when fostered with controls
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respiratory system
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• mild signs of chronic lung inflammation, such as increased granulocyte number and reduced surfactant protein D expression, are observed
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• at 11-14 weeks of age, the volume density and thickness of alveolar septa are increased to ~120% of those in heterozygous control animals
• the number of alveoli is significantly reduced by 20% relative to that in heterozygous control animals, indicating alveolar simplification
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• at 11-14 weeks of age, the volume density of alveolar ductal space is reduced to 91% of that in heterozygous control animals
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• at 11-14 weeks of age, the thickness of alveolar septa is increased to ~120% of those in heterozygous control animals
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• at 11-14 weeks of age, tidal midexpiratory flow is significantly reduced relative to that in heterozygous controls
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• at 11-14 weeks of age, respiratory frequency (breaths/min) is significantly reduced relative to that in heterozygous controls
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• at 11-14 weeks of age, airway hyperresponsiveness is observed in response to methacholine (MCh) provocation at doses of 0.125, 0.5, and 1.0 ug
• however, no significant differences are detected at MCh doses of 0.25 ug and above 1 ug
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• a minor downregulation of surfactant protein D expression is observed
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immune system
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• at 11-14 weeks of age, the number of granulocytes in lung is significantly increased relative to that in heterozygous control animals
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• mild signs of chronic lung inflammation, such as increased granulocyte number and reduced surfactant protein D expression, are observed
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hematopoietic system
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• at 11-14 weeks of age, the number of granulocytes in lung is significantly increased relative to that in heterozygous control animals
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cellular
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• exhibit aberrant migration of a subpopulation of rhombomere 4 (r4) neural crest cells into r3-adjacent cranial mesenchyme
• by E11, show aberrantly projecting axons extending through r3-adjacent mesenchyme, connecting the geniculate/cochleovestibular ganglion complex with the trigeminal ganglion
|
Analysis Tools