Analysis Tools
mortality/aging
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• homozygotes die between P1 and P3 days after birth, with only one male mouse surviving beyond weaning (P21); however, normal ratios are observed at E17-E19, indicating no embryonic lethality
• when mice are fed 5 mg N-acetylmannosamine (ManNAc) per ml water during matings, 12 homozygous pups survive beyond P3; 9/12 die between P6 and P12, with continued ManNAc treatment (until P21)
• the survivors remain smaller than littermates
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growth/size/body
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• by P2, animals are smaller than littermates, weighing only 70-100% of controls
• surviving pups with ManNAc treatment remain 70-100% weight of controls after birth
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renal/urinary system
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• at P2, kidneys display petechial hemorrhages
• red blood cell infiltrates are seen in the proximal and distal convoluted tubules and the collecting ducts
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• all mice dying by P3 show increased urinary protein
• single male mouse surviving past weaning shows increased urinary protein (>500 mg/dl protein), indicating renal disease
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• glomeruli contain red blood cell infiltrates in Bowman space; 64% are affected compared to 2% in heterozygotes and 4% of wild-type kidneys
• reduced infiltrates are observed in animals following ManNAc treatment
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• at P2, homozygotes exhibit podocytopathy likely due to hyposialylation of specific membrane glycoproteins
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• at P2, podocyte foot processes are largely fused
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• at P2, podocyte foot processes are flattened and largely fused with only a few wide foot processes remaining
• with ManNAc treatment, there is less podocyte flattening and fusion in mutant kidneys
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• at P2, filtration slits are reduced in number, abnormal in shape and position, and exhibit formation of tight junction-like structures
• number of filtration slits is improved with ManNAc treatment, although some still form tight junctions
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• at P2, the GBM displays segmental splitting of the lamina densa due to hyposialylation
• GBM integrity is improved with ManNAc treatment, although occasional segmental splitting is still observed
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• single surviving male homozygote euthanized at 8.5 months showed kidney changes consistent with glomerulopathies
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• single surviving male homozygote euthanized at 8.5 months showed severe bilateral hydronephrosis
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• red blood cell infiltrates are observed in proximal and distal convoluted tubules and collecting ducts
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• at P2, kidneys appear normal in size and shape, but histologically show cystic tubular dilatation
• with ManNAc treatment, there are fewer cystic tubular dilatations observed in cortex and medulla at P2
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cardiovascular system
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• at P2, kidneys display petechial hemorrhages
• red blood cell infiltrates are seen in the proximal and distal convoluted tubules and the collecting ducts
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homeostasis/metabolism
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• single male mouse surviving past weaning shows elevated BUN levels (39 mg/dl versus 21 mg/dl in wild-type controls)
• however, other serum metabolites, including creatinine and creatine kinase, are within normal range
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• all mice dying by P3 show increased urinary protein
• single male mouse surviving past weaning shows increased urinary protein (>500 mg/dl protein), indicating renal disease
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muscle
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• homozygotes show no morphological abnormalities in skeletal muscle compared to control littermates
• no abnormalities are observed in other tissues, such as heart or liver
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behavior/neurological
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• at P2, a prominent milkspot is sometimes absent
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