Phenotypes associated with this allele
reproductive system
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• large numbers of lipid drops present at 10 days and 7 weeks
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• spermatozoa still present at 7 weeks
• progressive degeneration of seminiferous tubules from 9-11 weeks
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• testicular weight 30-40% of normal controls at 14 weeks
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• 6-13 week old males mate but fail to sire offspring
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endocrine/exocrine glands
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• large numbers of lipid drops present at 10 days and 7 weeks
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• spermatozoa still present at 7 weeks
• progressive degeneration of seminiferous tubules from 9-11 weeks
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• testicular weight 30-40% of normal controls at 14 weeks
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cnptm1(cre)Kan mutation
(0 available);
any
Cnp mutation
(26 available)
Pex5tm1Pec mutation
(2 available);
any
Pex5 mutation
(29 available)
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mortality/aging
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• 91% are dead by 12 months of age
• none survive past 13 months
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behavior/neurological
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• hind limb tremors develop after 12 months
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• hind limb ataxia in about 14% of mice by 3 months of age
• symptoms most obvious after 9 months
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• hind limb paralysis develops eventually
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• hind limb paresis develops over 12 months
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nervous system
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• defects seen in rostral white matter by 4 months of age
• defects in the hippocampal commissure and cerebellar white matter less extensive
• defects become more extensive with time
• subcortical white matter degeneration increases as behavioral disorders progress
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• defective peroxisomes in oligodendrocytes
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• massive gliosis in areas of demyelination
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• activated microglia and macrophage appear early
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• axonal swelling appears early in the corpus callosum and spinal cord
• gradual loss of myelinated nerve fibers
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• very long chain fatty acids become progressively increased in myelin
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respiratory system
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• difficulty breathing develops after 12 months
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skeleton
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• becomes prevalent in mice over 12 months of age
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immune system
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• activated microglia and macrophage appear early
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• infiltration of T cells into demyelinated regions of the brain by 4 months
• B cell infiltration sometimes seen as well
• proinflammatory proteins become more abundant
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hematopoietic system
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• activated microglia and macrophage appear early
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growth/size/body
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• 30-40% lower than controls by 7 weeks of age
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• low body weight recovers to near normal between 7 weeks and 3 months
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• growth retardation starting about the third week after birth
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• hepatomegaly at 10 weeks
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• hypertrophic and hyperplastic hepatocytes particularly in pericentric region
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liver/biliary system
|
N |
• mice appear healthy and fertile with normal liver function through 14 months of age
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• possible compression of liver sinusoids
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• hepatomegaly at 10 weeks
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• hypertrophic and hyperplastic hepatocytes particularly in pericentric region
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• increased incidence after 12 months
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cellular
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• proliferation of smooth endoplasmic reticulum
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• tubulation of inner membrane
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• reduced numbers of curled and stacked cristae
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• proliferation of pleomorphic mitochondria
• mitochondria are normal if catalase positive peroxisomes are present
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• groups of lysoosomes as well as lipid drops observed
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• impaired respiratory chain
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• activity of mitchondrial complex II and IV are normal in the liver
• activity of mitochondrial complex I is less than 15% of normal in the liver at 20 weeks of age
• activity of citochondria complex III and V about 40% normal
• reduced membrane potential of liver mitochondria
• reduced ATP production
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• beta oxidation in cultured hepatocytes is abnormal
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homeostasis/metabolism
neoplasm
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• increased incidence after 12 months
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Analysis Tools