Analysis Tools
mortality/aging
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• mice begin to die at P5 and no mice survive beyond P24
|
growth/size/body
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• teeth are chalky white and chip easily
|
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• at birth about 25% of mice are smaller than heterozygotes
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• at birth about 25% of mice are smaller than heterozygotes
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• severe
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• 1.30 +/- 0.39% of body weight compared to 0.46 +/- 0.03% in wild-type controls
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digestive/alimentary system
coiled cecum
(
J:120867
)
|
• P12-P21 mice have small, corkscrew ceca regardless of impaction status
|
small cecum
(
J:120867
)
|
• P12-P21 mice have small, corkscrew ceca regardless of impaction status
|
constipation
(
J:120867
)
|
• mice that survive to at least P20 about 80% of mice have mild to severe intestinal impaction in the terminal ileum, cecum and colon
• however, mice that die much earlier have no bowel obstructions
|
|
• mice that survive to at least P20 have mild to severe intestinal impaction in the terminal ileum, cecum and colon
• however, mice that die much earlier have no bowel obstructions
|
homeostasis/metabolism
| N |
• plasma Na+ and K+ concentrations and urine osmolarity are relatively normal at P8 and no bicarbonaturia is observed
|
|
• altered expression of multiple proteins involved in proximal kidney tubule ammonia metabolism
• significantly reduced expression of phosphate-dependent glutaminase (PDG) and phosphoenolpyruvate carboxykinase, key enzymes in proximal tubule ammonia generation, with very weak PEPCK immunolabeling in proximal tubules
• significantly increased expression of glutamine synthetase, an enzyme that recycles intrarenal ammonia and regenerates glutamine, in proximal kidney tubule cells
• normal expression and localization of key proteins involved in collecting duct ammonia transport (rhesus B glycoprotein and rhesus C glycoprotein)
|
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• significant suppression of ammonia excretion at P8, greater than that observed in heterozygous mutant mice
• however, ability to lower urinary pH is intact or even accentuated
|
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• levels are sharply increased
|
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• increase in amiloride-sensitive sodium absorption in the proximal and distal colons
• increase in maximal sodium absorption in response to cAMP stimulation in Ringer solution
• increase in bumetanide-sensitive sodium absorption
• however, there is no difference in SITS-sensitive or residual camp-stimulated sodium absorption and there is no difference in sodium absorption in chloride free solutions
|
|
• 5.3 +/- 0.5mM compared to 22.3 +/- 0.5mM in wild-type controls
(J:120867)
• at P8, plasma bicarbonate levels average 10.3 +/- 0.6 mmol/l compared with 26.4 +/- 1.0 mmol/l in wild-type controls
(J:279694)
|
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• mild reduction (135.7 +/- 2.5mM compared to 143.0 +/- 1.7mM in controls)
|
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• spontaneous metabolic acidosis at P8
|
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• acidic urine pH at P8, with significantly lower pH than that observed in heterozygous mutant mice
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hematopoietic system
|
• 1.30 +/- 0.39% of body weight compared to 0.46 +/- 0.03% in wild-type controls
|
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• smaller and fewer megakaryocytes per field at x40 in the spleen (1.05 +/- 0.40 compared to 2.73 +/- 0.31 in wild-type controls)
|
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• 0.30 +/- 0.02 compared to 0.38 +/- 0.01 in wild-type controls
|
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• 7-fold increase in the percent of nucleated red blood cells
|
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• decrease in the relative numbers of lymphocytes to 63.7 +/- 2.1 compared to 77.4 +/- 4.0 in wild-type controls and increase in myelocytes to 35.3 +/- 1.9 compared to 21.4 +/- 3.6 in controls in peripheral blood
|
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• increase in red pulp
|
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• follicular organization is severely disrupted
|
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• increase in white pulp in which areas of lymphocytes predominant and smaller size of megakaryocytes are present
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skeleton
|
• skulls are very thin and virtually transparent
|
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• teeth are chalky white and chip easily
|
renal/urinary system
|
• significant suppression of ammonia excretion at P8, greater than that observed in heterozygous mutant mice
• however, ability to lower urinary pH is intact or even accentuated
|
|
• acidic urine pH at P8, with significantly lower pH than that observed in heterozygous mutant mice
|
|
• mild dilation of some collecting duct segments in the renal cortex at P8
• however, proximal kidney tubule morphology and overall renal anatomy appear normal
|
immune system
|
• 1.30 +/- 0.39% of body weight compared to 0.46 +/- 0.03% in wild-type controls
|
|
• decrease in the relative numbers of lymphocytes to 63.7 +/- 2.1 compared to 77.4 +/- 4.0 in wild-type controls and increase in myelocytes to 35.3 +/- 1.9 compared to 21.4 +/- 3.6 in controls in peripheral blood
|
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• increase in red pulp
|
|
• follicular organization is severely disrupted
|
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• increase in white pulp in which areas of lymphocytes predominant and smaller size of megakaryocytes are present
|
craniofacial
|
• skulls are very thin and virtually transparent
|
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• teeth are chalky white and chip easily
|
integument
nervous system
| N |
• despite mental retardation in human patients mice have morphologically normal brains
|
vision/eye
| N |
• despite ocular defects in human patients mice have morphologically normal eyes
|
