Analysis Tools
mortality/aging
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• despite normal Mendelian ratios at E18.5, fewer than expected mice are present at P10
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hematopoietic system
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• at P14, Iba-1-positive cells, which normally reside in the inner eye, are found both in the ONL and subretinal space, and appear more rounded and less ramified than in wild-type controls, indicating microglia activation
• microarray analysis of P13 eye cups revealed up-regulation of genes of the microglia/interferon pathway
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growth/size/body
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• in male mice fed standard chow or a high fat diet
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• at 2 weeks of age
(J:194781)
• ~50% reduction in body weight at 4 weeks of age
(J:234197)
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• in male mice fed a high diet
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homeostasis/metabolism
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N |
• mice exhibit normal glycemia, lipolysis, high fat diet-induced glucose-intolerance and temperature regulation during cold challenge
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• in male mice fed a high diet
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• in fed mice
• however, fasted mice exhibit normal respiratory quotient
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• microarray analysis of P13 eye cups revealed up-regulation of lipogenic and cholesterogenic genes, likely adaptations to loss of lysophosphatidylcholine (LPC) transport
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• increased in brown adipose tissue
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• at 8 weeks of age, mice show a >40% decrease in total steady-state levels of docosahexaenoic acid (DHA), but not other long chain fatty acids, in whole eye phospholipids, relative to wild-type controls
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• at 8 weeks of age, mice show moderately increased levels of arachidonic acid in whole eye phospholipids relative to wild-type controls
• very long chain unsaturated fatty acid (VLCFA) species of 40:5, 40:3, 38:3, and 38:2 are also moderately increased in eye phospholipids
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• in brown adipose tissue
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• in fasted male mice
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behavior/neurological
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• in fasted mice
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• in fasted mice
• however, mice fed ad libitum exhibit normal activity
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adipose tissue
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• in male mice fed standard chow or a high fat diet
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liver/biliary system
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• decreased liver VLDL triglyceride production after 20 hr of fasting
• however, levels are normal after 4 hr of fasting
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• in fasted mice
• however, mice fed a high fat diet exhibit normal hepatosteatosis
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nervous system
| N |
• surprisingly, homozygotes exhibit no disruption of blood-retinal barrier (BRB) and blood-brain barrier (BBB) integrity
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• at 4 months of age, the photoreceptor OS is shorter than in wild-type controls
• reduced OS length is seen as early as P13
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• as early as P13, mice exhibited a specific reduction in outer rod segment length
• outer rod segment discs appear disorganized and misfolded
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• at 4 months of age, the photoreceptor outer segment appears disorganized and thinner than normal
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• at 4 weeks of age, mice show a 77% reduction of radiolabeled LPC-[14C]DHA uptake in the brain relative to wild-type controls
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• at P14, Iba-1-positive cells, which normally reside in the inner eye, are found both in the ONL and subretinal space, and appear more rounded and less ramified than in wild-type controls, indicating microglia activation
• microarray analysis of P13 eye cups revealed up-regulation of genes of the microglia/interferon pathway
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vision/eye
| N |
• at 4 months of age, electroretinography revealed only slight, non-significant reductions in visual function relative to wild-type controls
• several key proteins involved in phototransduction and in retinol metabolism remain unaffected
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• at 4 months of age, the photoreceptor OS is shorter than in wild-type controls
• reduced OS length is seen as early as P13
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• as early as P13, mice exhibited a specific reduction in outer rod segment length
• outer rod segment discs appear disorganized and misfolded
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• at 4 months of age, the photoreceptor outer segment appears disorganized and thinner than normal
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• at 4 months of age, villi on the apical membranes of the RPE appear collapsed and not interacting with the OS, whereas villi of the wild-type RPE are extended and in close contact with OS
• at 4 months of age, villi on the basal membrane of the RPE appear edematous, unlike in wild-type controls
• at P13, villi at the RPE apical membrane appear thickened while basal infoldings appear edematous
• apical villi are disorganized both at P13 and at 5 months of age
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• at 4 months of age, mice exhibit a reduction in overall eye size relative to wild-type controls
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• at 4 months of age, retinas lack a clear limiting membrane between the ONL and inner segment and exhibit visibly reduced amounts of nuclei
• at P14, Iba-1-positive cells, which normally reside in the inner eye, are found both in the ONL and subretinal space, and appear more rounded and less ramified than in wild-type controls, indicating microglia activation
• at P14, rhodopsin, which normally resides in the OS, is mislocalized to the ONL consistent with defects in rhodopsin trafficking
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• at 4 months of age, the retinal ONL appears disorganized
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• at 4 months of age, retinas show some ONL loss due to photoreceptor degeneration
• rhodopsin levels are reduced as early as P13 before loss of ONL and remain low in adult mice
• however, ONL length is normal at P13
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• mice exhibit a slow, progressive form of retinal degeneration that primarily manifests as a reduction in OS length as early as P13
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• in some cases, large gaps are observed in the subretinal space along with phagocytic cells containing OS discs in endosomes, suggestive of microglia in the outer retina
• at P14, Iba-1-positive cells, which normally reside in the inner eye, are found both in the ONL and subretinal space, and appear more rounded and less ramified than in wild-type controls, indicating microglia activation
• microarray analysis of P13 eye cups revealed up-regulation of genes of the microglia/interferon pathway
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• at 4 weeks of age, mice show a >50% reduction of radiolabeled LPC-[14C]DHA uptake in the eyes relative to wild-type controls
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pigmentation
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• at 4 months of age, villi on the apical membranes of the RPE appear collapsed and not interacting with the OS, whereas villi of the wild-type RPE are extended and in close contact with OS
• at 4 months of age, villi on the basal membrane of the RPE appear edematous, unlike in wild-type controls
• at P13, villi at the RPE apical membrane appear thickened while basal infoldings appear edematous
• apical villi are disorganized both at P13 and at 5 months of age
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cellular
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• increased in brown adipose tissue
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immune system
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• at P14, Iba-1-positive cells, which normally reside in the inner eye, are found both in the ONL and subretinal space, and appear more rounded and less ramified than in wild-type controls, indicating microglia activation
• microarray analysis of P13 eye cups revealed up-regulation of genes of the microglia/interferon pathway
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