mortality/aging
• most homozygotes die within 12-24 hrs of birth, possibly due to renal failure
• however, homozygotes can survive for up to 72 hrs (without growing normally) when their bladders are emptied by external pressure
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growth/size/body
• although neonates (4-6 hrs) are of normal size and weight, P3 homozygotes fail to gain weight to the same extent as wild-type littermates
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renal/urinary system
• prolonged activation by KCl depolarisation of intact bladder preparations from homozygous mutant neonates indicates absence of the initial transient state of of high force generation and maximal shortening velocity (phase 1)
• in contrast, phase 2, a subsequent sustained state characterized by low force generation and maximal shortening velocity remains normal, suggesting that in neonatal smooth muscle phase 1 is generated by recruitment of smooth-muscle myosin heavy chain (MHC), whereas phase 2 can be generated by activation of non-muscle MHC
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• at ~9 hrs after birth, homozygotes show a filled, giant, thin-walled bladder
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• at ~9 hrs after birth
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muscle
• newborn homozygotes exhibit a dilative cardiomyopathy, putatively due to a 3-hr delay in ductus arteriosus closure
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• milk obtained from mothers remains in the stomach and upper duodenum, probably as a result of reduced intestinal movement
• low intestinal motility is probably responsible for starvation in growth-impaired neonates
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• prolonged activation by KCl depolarisation of intact bladder preparations from homozygous mutant neonates indicates absence of the initial transient state of of high force generation and maximal shortening velocity (phase 1)
• in contrast, phase 2, a subsequent sustained state characterized by low force generation and maximal shortening velocity remains normal, suggesting that in neonatal smooth muscle phase 1 is generated by recruitment of smooth-muscle myosin heavy chain (MHC), whereas phase 2 can be generated by activation of non-muscle MHC
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cardiovascular system
• newborn homozygotes display a 3-hr delay in ductus arteriosus closure relative to wild-type littemates
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• newborn homozygotes display a giant left ventricular cavity
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• newborn homozygotes exhibit a thin free left ventricular wall relative to wild-type mice
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• newborn homozygotes exhibit a dilative cardiomyopathy, putatively due to a 3-hr delay in ductus arteriosus closure
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• elevated plasma renin levels indicate that mean arterial blood pressure may be severely reduced
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homeostasis/metabolism
• newborn homozygotes exhibit a ~4-fold increase in plasma renin levels relative to wild-type mice
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digestive/alimentary system
• milk obtained from mothers remains in the stomach and upper duodenum, probably as a result of reduced intestinal movement
• low intestinal motility is probably responsible for starvation in growth-impaired neonates
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integument
cellular
• newborn homozygotes display a 3-hr delay in ductus arteriosus closure relative to wild-type littemates
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