Analysis Tools
mortality/aging
| N |
• Background Sensitivity: survival of homozygotes (F2-F4 generations) to weaning is most severely reduced on an inbred 129S/SvEv genetic background (3% vs expected 25%), and ameliorated on a mixed 129S6/SvEvTac x C57BL/6J genetic background (13%) relative to that observed on a mixed 129S6/SvEvTac x BALB/cByJ background (9%)
|
|
• on a mixed (129S6/SvEvTac x BALB/cByJ) genetic background, only 9% of homozygotes (F2-F4 generations) obtained by heterozygous intercrosses survive to weaning
• pre-weaning lethality is mostly attributed to severe cardiac valve and outflow tract defects
|
cardiovascular system
|
• starting at 6 weeks, all homozygotes exhibit aortic ossification with notable cartilaginous metaplasia and trabeculation of the aortic media
|
|
• valve hyperplasia is associated with an excess of specialized mesenchymal cells during endocardial cushion transformation
|
|
• a subset of homozygotes exhibit abnormal septation of the outflow tract, leading to a severely narrowed ascending aorta and an enlarged pulmonary trunk or the reverse
• starting at 6 weeks, all homozygotes exhibit abnormal ossification of the cardiac outflow tracts, never observed in wild-type mice
|
|
• occasionally, homozygotes display subepicardial vascular malformations in the ventricular wall with loss of the multiple smooth muscle cell layers in large vessels
|
|
• occasional thickening of the endocardium
|
|
• at birth, all homozygotes show cardiac valve hyperplasia of variable severity
• valve hyperplasia is associated with an excess of specialized mesenchymal cells during endocardial cushion transformation
|
|
• adult homozygotes exhibit extremely hyperplastic mitral valves
|
|
• moribund homozygotes exhibit extremely hyperplastic pulmonary valves
|
|
• homozygotes display impaired blood flow due to observed valve defects and abnormal vascular tone
|
|
• adult male homozygotes exhibit a significantly increased mean arterial pressure in the femoral artery relative to age-matched wild-type males
|
|
• ex vivo measurements of aortic contractility indicate that de-endothelialized mutant aortic rings show a normal response to phenylephrine; however, intact mutant rings exhibit increased contractility with no evidence of a basal endothelial relaxing activity
|
|
• phenylephrine-prestimulated mutant aortic rings show significantly reduced endothelium-dependent vascular relaxation in response to acetylcholine relative to similarly treated wild-type aortic rings
|
homeostasis/metabolism
|
• surviving homozygotes display occasional thrombotic lesions as well as focal ischemia in the lung, liver and kidney
|
muscle
|
• phenylephrine-prestimulated mutant aortic rings show significantly reduced endothelium-dependent vascular relaxation in response to acetylcholine relative to similarly treated wild-type aortic rings
|
