Phenotypes Associated with This Genotype

Genotype
MGI:6390207

• Allelic Composition: Pex1^tm1.1Hrw/Pex1^tm1.1Hrw
• Genetic Background: involves: C57BL/6NTac

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

mortality/aging

decreased survivor rate ( J:278655 )

• approximate 20% survival rate after P20

lethality during fetal growth through weaning, incomplete penetrance ( J:278655 )

• embryonic and/or perinatal loss is seen

postnatal lethality, incomplete penetrance ( J:278655 )

• about 75% of mice die before P20, with 90% survival after the first 20 days

growth/size/body

decreased body size ( J:278655 )

• pups are smaller at P3 but not P0

postnatal growth retardation ( J:278655 )

• both males and females show growth delay in the first 100 postnatal days beginning at P3

• growth delay remains throughout life

enlarged liver ( J:278655 )

• hepatomegaly at 3 and 6 months of age

liver/biliary system

bile duct proliferation ( J:278655 )

• P15 livers show bile duct proliferation

liver inflammation ( J:278655 )

• P15 livers show numerous inflammatory cells

abnormal liver morphology ( J:278655 )

• livers exhibit aberrant mitochondria, including swollen mitochondria with abnormal cristae and no peroxisomes

• accumulation of bile pigment in livers at P0 but not at later stages

enlarged liver ( J:278655 )

• hepatomegaly at 3 and 6 months of age

decreased liver glycogen level ( J:278655 )

• decrease in glycogen in the liver at P10, P15 and 3 months of age

increased liver cholesterol level ( J:278655 )

• liver tissues show accumulation of small vesicles composed of triglycerides/cholesterol esters at 3 and 6 months of age

increased liver triglyceride level ( J:278655 )

• liver tissues show accumulation of small vesicles composed of triglycerides/cholesterol esters at 3 and 6 months of age

hepatic necrosis ( J:278655 )

• P15 livers shows single cell necrosis, bile duct proliferation and numerous inflammatory cells

increased liver adenoma incidence ( J:278655 )

• 3 month old livers show early stages of cellular dysplasia and by 6 months, livers show a transition of normal hepatocytes to a focus of cellular alternation with increased nucleus-cytoplasm ratio indicating hepatic adenoma

liver fibrosis ( J:278655 )

• 3 and 6 month old livers show fibrosis

cholestasis ( J:278655 )

• cholestatic liver

homeostasis/metabolism

hyperglycemia ( J:278655 )

• plasma glucose levels are decreased at P0 and P5, indicating hyperglycemia

abnormal venous thrombosis ( J:278655 )

• intravascular coagulation and formation of thrombi with complete occlusion of the veins at different sites of the body at different ages

decreased liver glycogen level ( J:278655 )

• decrease in glycogen in the liver at P10, P15 and 3 months of age

abnormal bile salt homeostasis ( J:278655 )

• defective bile acid biosynthesis

• elevations of unconjugated and tauro-conjugated C24-bile acids in the liver at all ages

• elevations of unconjugated C27-bile acids and decreased levels of tauro-conjugated C24-bile acids in plasma at P10 but not in adults

• C27-bile acids in the liver primarily occur in the unconjugated form

• unconjugated C27-bile acid intermediates are increased in plasma, spleen, heart, and kidney but not detectable in the brain at 3 and 6 months of age

increased liver cholesterol level ( J:278655 )

• liver tissues show accumulation of small vesicles composed of triglycerides/cholesterol esters at 3 and 6 months of age

abnormal fatty acids level ( J:278655 )

• elevations in levels of C26:0 very long chain fatty acids and increased C26:0/C22:0 ratios in the liver

• elevations in levels of C26:0-lysophosphatidylcholine

• levels of branched-chain fatty acids phytanic and pristanic acid are increased in livers of 3 and 6 month old mice

• levels of poly-unsaturated fatty acid docosahexaenoic acid are reduced in most tissues at all ages

abnormal phospholipid level ( J:278655 )

• plasmalogen levels are lower in livers at P0 but not at other times

increased liver triglyceride level ( J:278655 )

• liver tissues show accumulation of small vesicles composed of triglycerides/cholesterol esters at 3 and 6 months of age

immune system

phlebitis ( J:278655 )

• venous vascular wall inflammation

liver inflammation ( J:278655 )

• P15 livers show numerous inflammatory cells

behavior/neurological

weakness ( J:278655 )

• pups appear very weak at P3

• however, pups have normal milk spots in their stomachs

cardiovascular system

phlebitis ( J:278655 )

• venous vascular wall inflammation

cellular

abnormal mitochondrial crista morphology ( J:278655 )

• livers exhibit swollen mitochondria with abnormal cristae

dilated mitochondrion ( J:278655 )

• swollen mitochondria in livers

abnormal peroxisome morphology ( J:278655 )

• no peroxisomes are seen in P5 livers, although they contain tiny vesicles

abnormal mitochondrial physiology ( J:278655 )

• decrease in the activities of respiratory chain complex I and complex II in the liver whereas activities of complex II and IV remain unchanged

endocrine/exocrine glands

bile duct proliferation ( J:278655 )

• P15 livers show bile duct proliferation

neoplasm

increased liver adenoma incidence ( J:278655 )

• 3 month old livers show early stages of cellular dysplasia and by 6 months, livers show a transition of normal hepatocytes to a focus of cellular alternation with increased nucleus-cytoplasm ratio indicating hepatic adenoma

renal/urinary system

hydronephrosis ( J:278655 )

• nearly all mice show unilateral hydronephrosis at all ages

reproductive system

reproductive system phenotype ( J:278655 )

N • males are fertile and are able to produce offspring after about 5 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Zellweger syndrome		DOID:905		J:278655