Analysis Tools
growth/size/body
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• a defect in insulin-regulated lipogenesis contributes to the lean phenotype
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homeostasis/metabolism
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• ligation of the common carotid artery causes a significant increase in neointimal lesion formation compared to wild-type mice
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• mouse embryonic fibroblasts (MEFs) and macrophages under normal conditions or loaded with cholesterol contain reduced free cholesterol but increased esterified-cholesterol content
• however, when cholesterol loaded, macrophages show an increase in total cellular cholesterol content
• cellular cholesterol efflux not affected although ABCA1-mediated cholesterol efflux is more sensitive to the inhibitory effects of glyburide in macrophages
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• post-prandial serum levels of insulin were increased in mice that had been on a high fat diet for 9 months
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• interstitial cells of Cajal and smooth muscles of the intestine (longitudinal muscles) show reduced responsiveness to endogenous and exogenous nitric oxide
• N-omega-nitro-L-arginine is ineffective to inhibit intestinal relaxation and exogenous nitric oxide donor sodium nitroprusside relaxes longitudinal muscle less than in controls
• apamin significantly reduces small intestinal tissue relaxation to electrical field stimulation in nonadrenergic noncholinergic conditions in mutants but not controls indicating that the normal spontaneous contraction of intestinal muscle is probably maintained by increased activity of apamin-sensitive mediators
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• mutants show a blunted decline in glucose levels upon insulin injection
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• serum nonesterified fatty acid levels fail to rise in mutants in response to prolonged fasting
• mutants exhibit a 5-fold reduction in their lipolytic response to a beta3-specific adrenergic receptor agonist
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• mutants show a slower wound healing rate when circular punch biopsies are done on the back skin compared to wild-type
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cardiovascular system
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• lung capillaries exhibit smaller tight junctions and abnormalities in capillary endothelial cell adhesion to the basement membrane
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• large increase in microvascular permeability as indicated by an increased rate of clearance for iodinated serum albumin from the circulatory system and lower levels of endogenous serum albumin
• paracellular movement of Ruthenium Red is increased in lung endothelial cells indicating hyperpermeable tight junctions/capillaries
• treatment with L-NAME, a nitric-oxide synthasae inhibitor, restores normal microvascular permeability
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• at pressures between 30 and 70 mmHg, cerebral arteries develop less myogenic tone than wild-type, indicating attenuated pressure-induced constriction
• pressure induces a smaller depolarization and smaller arterial wall intracellular calcium elevation in mutant cerebral arteries than in wild-type, resulting in reduced myogenic constriction
• membrane depolarization induced by 60 mM potassium results in attenuated arterial wall intracellular calcium elevation and constriction in cerebral arteries
• N-omega-nitro-L-arginine, a nitric oxide synthase inhibitor, does not restore myogenic tone in cerebral arteries, indicating that NOS activation and nitric oxide generation do not significantly contribute to the attenuated myogenic response
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• ligation of the common carotid artery causes a significant increase in neointimal lesion formation compared to wild-type mice
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adipose tissue
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• perigonadal adipocytes completely lack an electron-dense thick band of material that surrounds the normal lipid droplet
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cellular
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• protrusive and retractile activities at cell edges are higher in MEFs and protrusions and retractions occurs throughout the cell perimeter instead of protrusions in the direction of movement and retractions in the rear end as in wild-type MEFs
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• mouse embryonic fibroblasts (MEFs) lose polarity when plated on fibronectin, exhibiting a round shape with aberrant actin cytoskeleton architecture
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• microtubule organizing center reorientation toward the leading edge of a wound is reduced in MEFs
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• absence of caveolae in vascular smooth muscle cells
(J:115492)
• caveolae are absent in the longitudinal muscles of the intestine
(J:114334)
• chondrocytes lack caveolae
(J:128103)
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• MEFs plated on fibronectin move faster and exhibit impaired directional migration compared to wild-type MEFs
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• wound closure and chemotactic response of MEFs in a transwell assay are impaired
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• mouse embryonic fibroblasts (MEFs) and macrophages under normal conditions or loaded with cholesterol contain reduced free cholesterol but increased esterified-cholesterol content
• however, when cholesterol loaded, macrophages show an increase in total cellular cholesterol content
• cellular cholesterol efflux not affected although ABCA1-mediated cholesterol efflux is more sensitive to the inhibitory effects of glyburide in macrophages
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skeleton
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• at 8 weeks of age, cartilage extends into the epiphyseal bone and metaphyseal marrow
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• increase in the number of columns of cells in the proliferating cell zone
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• increase in the number of columns of cells in the hypertrophic cell zone of growth plates
• number of hypertrophic cells is increased for each column of cells
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• tibial growth plates are 12.3% longer than in wild-type
• costochondral growth plates are longer
• growth plates of femoral chondyles are extended, both vertically and in cross-section
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• metaphyseal bone volume is greater
• increase in number of trabeculae in metaphyseal bone
• at 8 weeks of age, in the metaphysis the trabeculae are coated with a thin layer of bone
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• cartilage of the costochondral junction is more cellular
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• increase in number of trabeculae in metaphyseal bone
• at 8 weeks of age, in the metaphysis the trabeculae are coated with a thin layer of bone
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• hyaline cartilage is more cellular, extending distally from the rib
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• growth zone chondrocytes fail to exhibit a response to 1,25-dihydroxyvitaminD3
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behavior/neurological
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• exploratory behavior in a new environment is reduced as early as 13 weeks of age
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• mutants exhibit spinning upon tail suspension; frequency and intensity of spinning increases progressively with age such that by 50 weeks, it is seen in 50% of mutants and in all mutants by 80-90 weeks of age
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• exhibit clasping as early as 20 weeks of age and the number of mutants that clasp increases with age
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• mutants exhibit impaired ability to hold and maneuver on a bar
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• mutants tend to stop and/or change direction of movement while traversing a tunnel more often than controls
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• wider overlap (distance between superimposed hindpaw and forepaw) that coincides with stride abnormalities
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• evident by 10 weeks of age
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• mutants are less active than their wild-type littermates
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nervous system
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• brains are smaller at 60 weeks of age but not at 11 weeks of age
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• the internal capsule fiber bundles are smaller in size in the striatum
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digestive/alimentary system
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• mutants exhibit impaired small intestinal nitric oxide function
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muscle
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• at pressures between 30 and 70 mmHg, cerebral arteries develop less myogenic tone than wild-type, indicating attenuated pressure-induced constriction
• pressure induces a smaller depolarization and smaller arterial wall intracellular calcium elevation in mutant cerebral arteries than in wild-type, resulting in reduced myogenic constriction
• membrane depolarization induced by 60 mM potassium results in attenuated arterial wall intracellular calcium elevation and constriction in cerebral arteries
• N-omega-nitro-L-arginine, a nitric oxide synthase inhibitor, does not restore myogenic tone in cerebral arteries, indicating that NOS activation and nitric oxide generation do not significantly contribute to the attenuated myogenic response
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