Phenotypes Associated with This Genotype

Genotype
MGI:2676371

• Allelic Composition: Pitpna^{Gt(OST1152)Lex}/Pitpna^{Gt(OST1152)Lex}
• Genetic Background: involves: 129S5/SvEvBrd

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

neonatal lethality, incomplete penetrance ( J:85204 )

• 40% died within 48 hours of birth

• neonatal death putatively a result of the cessation of nutrients provided by maternal circulation

postnatal lethality ( J:85204 )

• 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

abnormal abdominal fat pad morphology ( J:85204 )

• absence of axillary fat pads

abnormal inguinal fat pad morphology ( J:85204 )

• absence of inguinal fat pads

behavior/neurological

tremors ( J:85204 )

• coarse action tremors upon limb extension

ataxia ( J:85204 )

• by 4 days of age all mice were severely ataxic and unable to maintain themselves upright

seizures ( J:85204 )

• approximately 10% of mice exhibited spontaneous seizures

cellular

abnormal apoptosis ( J:85204 )

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

digestive/alimentary system

abnormal intestinal epithelium morphology ( J:85204 )

• intestinal microvesicular steatosis similar to that observed in human chylomicron retention disease

abnormal enterocyte morphology ( J:85204 )

• intestinal cells were larger than those of wild-type due to an accumulation of diet-derived lipids

abnormal intestinal lipid absorption ( J:85204 )

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:85204 )

• aberrant morphology of observed islets

decreased pancreatic islet number ( J:85204 )

• greater than 2-fold decrease in the absolute islet number relative to controls

growth/size/body

decreased body weight ( J:85204 )

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

postnatal growth retardation ( J:85204 )

homeostasis/metabolism

abnormal intestinal lipid absorption ( J:85204 )

increased circulating bilirubin level ( J:85204 )

• modest elevations consistent with the amount of hepatic stress

hypoglycemia ( J:85204 )

• 9-fold reduction in serum glucose levels relative to controls, accompanied by increased levels of gluconeogenic compounds

decreased circulating glucagon level ( J:85204 )

increased circulating corticosterone level ( J:85204 )

decreased circulating insulin level ( J:85204 )

• 9-fold reduction in serum insulin levels relative to controls

decreased circulating triglyceride level ( J:85204 )

increased circulating alkaline phosphatase level ( J:85204 )

• modest elevations consistent with the amount of hepatic stress

increased circulating aspartate transaminase level ( J:85204 )

decreased glycogen catabolism rate ( J:85204 )

• kinetic defects in the rate of glycogenolysis

abnormal vitamin E level ( J:85204 )

• 10-fold decrease in vitamin E in the brain

liver/biliary system

abnormal hepatocyte morphology ( J:85204 )

• aponecrosis of hepatocytes

microvesicular hepatic steatosis ( J:85204 )

• intracellular accumulation of neutral lipid and free fatty acid mass, resulting in microvesicular steatosis

nervous system

seizures ( J:85204 )

• approximately 10% of mice exhibited spontaneous seizures

abnormal brainstem morphology ( J:85204 )

abnormal cerebellum morphology ( J:85204 )

• degeneration indicated by reactive gliosis

abnormal Purkinje cell morphology ( J:85204 )

abnormal spinal cord morphology ( J:85204 )

• infiltration by inflammatory cells in the dorsal spinal column

abnormal spinal cord ventral horn morphology ( J:85204 )

• aponecrosis of motor neuron cell bodies in the ventral horn

abnormal spinal cord white matter morphology ( J:85204 )

• white matter was thin and sparse in regions of the cervical, lumbar, and thoracic spinal cord

neurodegeneration ( J:85204 )

• aponecrotic spinocerebellar disease characterized by reactive gliosis of the cerebellum and brainstem

• also affecting the white and gray matter of the spinal cord

demyelination ( J:85204 )

• observed in both white and gray matter, particularly in the dorsal spinal column

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
chylomicron retention disease		DOID:0060357	OMIM:246700	J:85204