Analysis Tools
homeostasis/metabolism
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• On either a regular chow or a HF/HC diet, homozygotes show no significant differences in plasma albumin, urea nitrogen, or creatinine levels relative to control C57BL/6 mice
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• on a regular chow diet, the plasma levels of apoA-I and apoA-II in mutant mice are reduced to 10% and 23%, respectively, of C57BL/6 control mice; in contrast, apoB levels remain unaffected
• on a HF/HC diet, the plasma levels of apoA-I and apoA-II are decreased to 17% and 50%, respectively, of C57BL/6 control mice; apoB levels are reduced to 45% of control levels
• notably, a subset of homozygotes fed a HF/HC diet for 16 weeks accumulate lipoprotein X; induction of apoC-containing LpX by the HF/HC diet is associated with the development of glomerulosclerosis in these mice
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• on a regular chow diet, the plasma levels of total cholesterol in mutant mice are reduced to 25% of C57BL/6 control mice
• on a HF/HC diet, the plasma levels of total cholesterol are decreased to 45% of C57BL/6 control mice
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• on a regular chow diet, the plasma levels of cholesteryl esters (CE) and HDL cholesterol in mutant mice are reduced to 7% and 14%, respectively, of C57BL/6 control mice; in contrast, non-HDL cholesterol levels remain unaffected
• on a HF/HC diet, the plasma levels of CE and HDL cholesterol are decreased to 44% and 6%, respectively, of C57BL/6 control mice; non-HDL cholesterol levels are reduced to 52% of control levels
• notably, homozygotes fed the atherogenic diet show a dramatic increase in the CE/total cholesterol ratio from 21 to 76% relative to control mice
• on the HF/HC, homozygotes show an increase in the mean diameter of the small spherical particles in the HDL size range; also, the % of discoidal particles in the HDL fraction decreases from 14 to 4% after the HF/HC diet
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• after 16 weeks on a HF/HC diet, homozygotes display a significant reduction in VLDL and IDL cholesterol levels relative to C57BL/6 control mice; VLDL density fractions are triglyceride-enriched
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• on a regular chow diet, the plasma levels of phospholipids in mutant mice are reduced to 54% of C57BL/6 control mice
• on a HF/HC diet, the plasma levels of phospholipids are decreased to 48% of C57BL/6 control mice
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• on a regular chow diet, the plasma triglyceride levels in mutant mice are increased by 50% relative to C57BL/6 control mice
• on the HF/HC diet, plasma triglycerides levels remain unchanged
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• after a HF/HC diet, the majority of urine samples collected from mutant mice exhibit proteinuria (data not shown)
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renal/urinary system
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• sporadic preglomerular arterioles contain periodic acid Schiff-positive droplets; however, no lesions of larger blood vessels are detected
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• after a HF/HC diet, the majority of urine samples collected from mutant mice exhibit proteinuria (data not shown)
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• after 16 weeks an a HF/HC diet, a subset of homozygotes presenting with lipoprotein X accumulate free cholesterol and polar lipids in glomeruli
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• after 16 weeks an a HF/HC diet, renal lesions in affected mutants show significant reductions in vascular space and an expanded mesangial region with an increased number of mesangial cells
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• after 16 weeks an a HF/HC diet, renal lesions in affected mutants show mesangial sclerosis and increased extracellular matrix with accumulation of lipid droplets and macrophages
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• after 16 weeks an a HF/HC diet, a subset of homozygotes accumulating lipoprotein X in their plasma develop glomerulosclerosis characterized by mesangial cell proliferation, sclerosis, lipid accumulation, and deposition of electron dense material throughout the glomeruli; no tubular or interstitial lesions are observed
• no glomerulosclerosis is detected on a regular chow diet or in mutant mice with no accumulation of lipoprotein X
• also, no alterations are noted in the peripheral basement membrane or podocytes; pedicels remain intact
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hematopoietic system
| N |
• in homozygotes, platelet counts, red blood cell indices (mean corpuscular volume and mean corpuscular hemoglobin), and plasma bilirubin levels remain normal
• dietary status (regular chow vs HF/HC) does not affect blood counts, hemoglobin, hematocrit, or bilirubin levels in mutant or control C57BL/6 mice
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• homozygotes develop a mild hemolytic anemia with normochromic normocytic indices
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• despite an absence of hyperbilirubinemia, homozygotes exhibit increased reticulocyte and target cell counts relative to control C57BL/6 mice
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• osmotic fragility tests indicate that mutant erythrocytes are more resistant to hemolysis than wild-type erythrocytes
• erythrocyte membrane fragility is decreased, consistent with altered erythrocyte membrane lipids as well as an increased proportion of target cells that are more resistant to hemolysis
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vision/eye
| N |
• after 16 weeks on a high-fat high-cholesterol (HF/HC) diet, homozygotes display no ocular abnormalities relative to control C57BL/6 mice
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cardiovascular system
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• sporadic preglomerular arterioles contain periodic acid Schiff-positive droplets; however, no lesions of larger blood vessels are detected
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cellular
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• after 16 weeks an a HF/HC diet, renal lesions in affected mutants show significant reductions in vascular space and an expanded mesangial region with an increased number of mesangial cells
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