Analysis Tools
behavior/neurological
|
• mice over 6 months show lower food consumption; this may be partly due to impeded food intake from the containers at the cage top and when food access is made easier at the cage floor, mice show increased food consumption but wild-type mice increase their food consumption too indicating that locomotor deficits may not be the only reason for weight differences
|
|
• mice develop hind limb clasping
|
|
• mice develop an unsteady gait progressively from 4 months of age to end of testing at 14 months
|
|
• mice develop problems in movement coordination progressively from 4 months of age to end of testing at 14 months
|
cellular
|
• mouse embryonic fibroblasts (MEFs) lack elongated peroxisomes compared to wild-type MEFs which contain heterogenous peroxisomes with spherical and elongated morphology
• however, peroxisome numbers are normal in MEFs and number, distribution, and morphology of peroxisomes in the soma of Purkinje cells are unchanged
• MEFs incubated with docosahexaenoic acid (DHA) to induce peroxisome elongation do not show an increase in elongated peroxisomes as in treated wild-type MEFs indicating impaired peroxisomal membrane expansion
• peroxisome numbers are elevated in hepatocytes of 3- and 15-month old mice, with a 3.3-fold increase in peroxisome numbers in hepatocytes at 3 months of age
• peroxisomes in hepatocytes show more heterogenous shapes than in wild-type controls and often localize in clusters
|
growth/size/body
|
• mice over 6 months of age show lower weights
|
hematopoietic system
|
• elevation in ramified microglia from 5 to 23% in cerebellar lobes, while microglia numbers increase only moderately, indicting a mild neuroinflammation
|
homeostasis/metabolism
|
• mice exhibit slightly elevated levels of lignoceric acid (C24:0) and 3-fold elevation in cerotic acid (C26:0) in plasma and tissues
• lipidomics of liver and cerebellum show tissue-specific alterations in distinct lipid classes and subspecies
• ether lipid formation is perturbed in liver towards an accumulation of alkyldiacylglycerols
|
|
• very long-chain fatty acid levels are elevated in almost all complex lipids
• unusual ultra-long chain fatty acids (C>32) are elevated in phosphocholines from cerebellum but not liver, indicating an organ-specific imbalance of fatty acid degradation and elongation
|
|
• liver shows increased levels of alkylmonoacylglycerols and alkyldiacylglycerols
|
|
• cerebellum shows reduced levels of alkylphosphatidylcholines and alkylphosphatidylethanolamines indicating diminished ether phospholipid levels
|
immune system
|
• elevation in ramified microglia from 5 to 23% in cerebellar lobes, while microglia numbers increase only moderately, indicting a mild neuroinflammation
|
|
• elevation in ramified microglia from 5 to 23% in cerebellar lobes, while microglia numbers increase only moderately, indicting a mild neuroinflammation
|
liver/biliary system
 |
• lipid droplets with a diameter of more than 2 um are increased in livers of 3-month old males, however, 15-month old males show reduced amounts of such large lipid droplets
• however, the liver does not exhibit obvious alterations
|
|
|
• peroxisome numbers are elevated in hepatocytes of 3- and 15-month old mice, with a 3.3-fold increase in peroxisome numbers in hepatocytes at 3 months of age
• peroxisome-ER contact sites are highly reduced in hepatocytes
• however, membrane associations between peroxisomes and mitochondria are not different
• peroxisome in triple associations connecting peroxisomes to mitochondria via an interjacent ER tubule are decreased from 27.5% to 2.8%
• peroxisomes in hepatocytes show more heterogenous shapes in than in wild-type controls and often localize in clusters
• hepatocytes contain large clusters of multiple spherical to oval-shaped peroxisomes devoid of other organelles and mitochondria are frequently surrounded by sheet-like ER structures underlining a subcellular separation between the peroxisomes and remaining organelles compared to wild-type in which peroxisomes are distributed as single or small groups of organelles which are individually surrounded by ER tubules
• the average minimum distance between peroxisome and ER is increased in hepatocytes
|
nervous system
|
• elevation in ramified microglia from 5 to 23% in cerebellar lobes, while microglia numbers increase only moderately, indicting a mild neuroinflammation
|
|
• elevation in ramified microglia from 5 to 23% in cerebellar lobes, while microglia numbers increase only moderately, indicting a mild neuroinflammation
|
|
|
• the distance between the soma and the axon initial segment is slightly, but significantly, increased in Purkinje cells
• however, axonal initial segment loss is not seen and axonal initial segment length is not different
|
|
|
• Purkinje cell numbers are reduced by 22 and 26% in cerebellar anterior lobes 3-6 and posterior lobes 7-9, respectively, in 1-year old males
|
|
• radial-type Bergmann glia undergo reactive gliosis, especially in places with missing Purkinje cells
|
|
|
• axon swellings are seen in anterior and posterior lobes of cerebellar granular layers
|
|
• progressive cerebellar neurodegeneration
|
|
• slight, but significant, cerebellar demyelination in 1-year old mice
|
reproductive system
|
• successful mating is not seen with breeding pairs older than 4 months
|
skeleton
vision/eye
|
• retinal degeneration characterized by reduced photoreceptor cells and increase in microglia and astrocyte activation
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| peroxisomal disease | DOID:906 | J:299448 | ||
