Mouse Genome Informatics
hm1
    Pitpnatm1Vab/Pitpnatm1Vab
involves: 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 40% died within 48 hours of birth
• neonatal death putatively a result of the cessation of nutrients provided by maternal circulation
• all but 1 mouse died by 11 days of age
• early postnatal death putatively a result of the cessation of nutrients provided by maternal circulation

adipose tissue
• absence of axillary fat pads
• absence of inguinal fat pads

behavior/neurological
• coarse action tremors upon limb extension
• by 4 days of age all mice were severely ataxic and unable to maintain themselves upright
• approximately 10% of mice exhibited spontaneous seizures

cellular
• increased apoptosis in the cerebellum, particularly in the external granule layer

digestive/alimentary system
• intestinal microvesicular steatosis similar to that observed in human chylomicron retention disease
• intestinal cells were larger than those of wild-type due to an accumulation of diet-derived lipids

endocrine/exocrine glands
• aberrant morphology of observed islets
• greater than 2-fold decrease in the absolute islet number relative to controls

growth/size
• by 10 days of age, surviving mice were 2.5 fold less massive than wild-type and heterozygous littermates

homeostasis/metabolism
• modest elevations consistent with the amount of hepatic stress
• 9-fold reduction in serum glucose levels relative to controls, accompanied by increased levels of gluconeogenic compounds
• 9-fold reduction in serum insulin levels relative to controls
• modest elevations consistent with the amount of hepatic stress
• kinetic defects in the rate of glycogenolysis

liver/biliary system
• aponecrosis of hepatocytes
• intracellular accumulation of neutral lipid and free fatty acid mass, resulting in microvesicular steatosis

nervous system
• approximately 10% of mice exhibited spontaneous seizures
• degeneration indicated by reactive gliosis
• infiltration by inflammatory cells in the dorsal spinal column
• aponecrosis of motor neuron cell bodies in the ventral horn
• white matter was thin and sparse in regions of the cervical, lumbar, and thoracic spinal cord
• observed in both white and gray matter, particularly in the dorsal spinal column
• aponecrotic spinocerebellar disease characterized by reactive gliosis of the cerebellum and brainstem
• also affecting the white and gray matter of the spinal cord

Mouse Models of Human Disease
OMIM IDRef(s)
Chylomicron Retention Disease; CMRD 246700 J:85204