Analysis Tools
mortality/aging
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• about 68% of homozygotes die beginning on P16-P18 and through P29
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behavior/neurological
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• when placed in a novel environment, homozygotes appear hesitant to move and explore their surroundings
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poor grooming
(
J:54705
)
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• within 16 hours of death, homozygotes exhibit varying degrees of a wax-like material primarily on the ventral surface of paws, around the eyes, inside the ear, on the chin, and within the back fur
• such material is not observed on living mutants, suggesting lack of normal grooming by the mutants prior to death
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• at 2 weeks, homozygotes begin to exhibit an ataxic gait that results in inability to move the hindlimbs
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• at 2 weeks, homozygotes display preconvulsant episodes that often end in a catatonic-like state resembling an absence seizure
• at death, homozygotes display a postmortem appearance suggestive of death by a convulsive seizure (forepaws in flexion)
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digestive/alimentary system
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• mutant gastric glands show a decrease in thickness of the whole gastric epithelium
• homozygotes have a widened lamina propria between the gastric glands and at the base of gastric epithelium
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• Na+/H+ exchanger activity is reduced >95% in acinar cells and >80% in duct cells isolated from mutant parotid glands
• mutant parotid saliva shows a significant increase in osmolality and sodium, potassium, and chloride content, indicating impaired NaCl absorption
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• relative to wild-type, homozygotes show a 34% reduction in the total volume of pilocarpine-stimulated saliva secreted over a 50-min collection period
• also, homozygotes show a significant reduction in the rate of saliva secretion: the flow rate reaches a 42% inhibition at the end of the 50-min period
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endocrine/exocrine glands
| N |
• homozygotes display normal parotid gland weight and morphology relative to wild-type
• parotid acinar cells from isoproterenol-treated homozygotes lack Na+/H+ exchanger activity
• however, in response to chronic beta1-adrenergic receptor stimulation, homozygotes show an isoproterenol-induced parotid gland hypertrophy in acinar cells that is comparable to that observed in wild-type
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• Na+/H+ exchanger activity is reduced >95% in acinar cells and >80% in duct cells isolated from mutant parotid glands
• mutant parotid saliva shows a significant increase in osmolality and sodium, potassium, and chloride content, indicating impaired NaCl absorption
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• relative to wild-type, homozygotes show a 34% reduction in the total volume of pilocarpine-stimulated saliva secreted over a 50-min collection period
• also, homozygotes show a significant reduction in the rate of saliva secretion: the flow rate reaches a 42% inhibition at the end of the 50-min period
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growth/size/body
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• at 2 weeks, homozygotes display a significant reduction in body weight relative to wild-type
• by 10 weeks, homozygotes weigh only ~18 g in contrast to the ~28 g characteristic of wild-type mice
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homeostasis/metabolism
| N |
• homozygotes display normal systemic acid-base homeostasis (pH, PCO2, PO2, and HCO-3) relative to wild-type
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• in the absence of an NHE1 inhibitor (eniporide), homozygotes are resistant to cardiac ischemia-reperfusion injury with significantly less impaired left ventricular developed pressure, end-diastolic pressure, and coronary flow as well as reduced cellular damage and LDH release and higher left ventricular ATP content relative to wild-type hearts
• notably, eniporide has no apparent effect on the degree of cardioprotection observed in mutant hearts
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• relative to wild-type, homozygotes show a 34% reduction in the total volume of pilocarpine-stimulated saliva secreted over a 50-min collection period
• also, homozygotes show a significant reduction in the rate of saliva secretion: the flow rate reaches a 42% inhibition at the end of the 50-min period
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reproductive system
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• homozygotes that reach adulthood are fertile and capable of breeding with wild-type or heterozygous mice
• no successful matings between male homozygotes and female homozygotes are observed
• female homozygotes mated with male heterozygotes are able to carry a litter to term; however, females that deliver subsequently die several days postpartum
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nervous system
| N |
• homozygotes show no changes in the appearance or number of Purkinje or granule cells of the folia of the cerebellum; the molecular layer is of normal thickness
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• at 2 weeks, homozygotes display preconvulsant episodes that often end in a catatonic-like state resembling an absence seizure
• at death, homozygotes display a postmortem appearance suggestive of death by a convulsive seizure (forepaws in flexion)
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cardiovascular system
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• homozygotes exhibit significantly lower heart weights relative to wild-type mice
• however, no significant differences in mean HW/BW ratios are observed with or without eniporide treatment, suggesting that smaller hearts are a result of growth retardation
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• in the absence of an NHE1 inhibitor (eniporide), homozygotes are resistant to cardiac ischemia-reperfusion injury with significantly less impaired left ventricular developed pressure, end-diastolic pressure, and coronary flow as well as reduced cellular damage and LDH release and higher left ventricular ATP content relative to wild-type hearts
• notably, eniporide has no apparent effect on the degree of cardioprotection observed in mutant hearts
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integument
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• homozygotes show a slight increase in keratin accumulation with small lipid droplets on the surface of the cornified layer
• these particles are roughly the same size as the small particles found on mutant skin
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• within 16 hours of death, homozygotes exhibit reduced thickness of the whole skin, including the epidermis, dermis, subcutaneous fat, and muscle
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