Analysis Tools
cardiovascular system
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• 50% of mice develop transverse aortic constriction (TAC)-induced aortic complications
• aortae following TAC show less thickening, with reduced medial and adventitial areas, compared to controls
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• aortic arches show decreased numbers of cells and cell density in the media at P1, 4 weeks, and 6 months of age
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• ascending aortae show decreased numbers of cells and cell density in the media at P1, 4 weeks, and 6 months of age
• however, no differences in the proximal and distal thoracic descending aorta are seen and there are no differences in the percentage of proliferating or apoptotic cells in the aortae
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• the ascending aorta of mice surviving TAC are significantly dilated compared to wild-type controls
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• mice exhibit altered aortic remodeling and rupture of the aorta after transverse aortic constriction (TAC)
• aortae following TAC show less thickening, with reduced medial and adventitial areas, compared to controls
• adventitial macrophage infiltration after TAC is attenuated in mutant aortae
• 2 weeks after TAC, apoptosis is increased in the aortic media and proliferation is decreased
• mice injected with a pharmacological inhibitor of Trp53, pifthirin-alpha, 24 hours before TAC and every 48 hours after TAC, show a reduction in the incidence of aortic rupture and intramural hematomas and normalized levels of apoptosis
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• smooth muscle cells explanted from ascending aortae are more sensitive to staurosporine-induced apoptosis than wild-type cells
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vision/eye
small pupil
(
J:101355
)
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• the corneal endothelial layer is absent
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• the corneal epithelium is thinner
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• the corneal stroma is disorganized
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• the anterior lens epithelium does not properly separate from the cornea preventing formation of the anterior chamber
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• at E14.5 vacuoles are present in the lens, the characteristic bow region normally formed by lens nuclei is less pronounced or absent, many nuclei are present in the posterior region of the lens, and a keratolenticular connection is seen
• at E14.5 and E17.5, premature differentiation of and reduced proliferation in the anterior lens epithelium is seen
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• at E10.5 the invaginating lens placode is smaller resulting in a smaller the lens at the lens vesicle stage
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• the lenses contain many vacuoles that disrupt the morphology
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• the lens epithelium does not properly separate from the cornea and is multilayered rather than a single layer as in wild-type mice
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• normal lens fibers do not form and are replaced with irregularly shaped nucleated cells with severe vacuolation
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• in some homozygotes the eyes never open
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retina fold
(
J:101355
)
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• the retina is abnormally folded resulting in shrinkage of the eye
• however, the retinal layers appear to be correctly specified
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homeostasis/metabolism
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• mice exhibit altered aortic remodeling and rupture of the aorta after transverse aortic constriction (TAC)
• aortae following TAC show less thickening, with reduced medial and adventitial areas, compared to controls
• adventitial macrophage infiltration after TAC is attenuated in mutant aortae
• 2 weeks after TAC, apoptosis is increased in the aortic media and proliferation is decreased
• mice injected with a pharmacological inhibitor of Trp53, pifthirin-alpha, 24 hours before TAC and every 48 hours after TAC, show a reduction in the incidence of aortic rupture and intramural hematomas and normalized levels of apoptosis
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mortality/aging
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• 4 of 14 mice die between 4 and 11 days after TAC compared to none of wild-type mice
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muscle
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• smooth muscle cells explanted from ascending aortae are more sensitive to staurosporine-induced apoptosis than wild-type cells
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nervous system
| N |
• no abnormalities in brain development are seen
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