Phenotypes Associated with This Genotype

Genotype
MGI:5607258

• Allelic Composition: Slc40a1^tm1.1Mmfe/Slc40a1^tm1.1Mmfe
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

mortality/aging

premature death ( J:215585 )

• begin to die from 7 months of age

homeostasis/metabolism

increased circulating ferritin level ( J:215585 )

• young adults exhibit high transferrin saturation and a marked increase in serum ferritin levels

decreased circulating unsaturated transferrin level ( J:215585 )

abnormal enzyme/coenzyme level ( J:215585 )

• reduction in levels of lytic pancreatic enzymes such as amylase and elastase

increased circulating lipase level ( J:215585 )

abnormal iron homeostasis ( J:215585 )

• iron overload in the liver, pancreas, kidney, heart, and brain, however zinc, copper, sodium, calcium, and phosphate levels are unaffected

increased heart iron level ( J:215585 )

• iron accumulates in the heart, mainly in vascular smooth muscle cells

decreased intestinal iron level ( J:215585 )

• intestinal epithelium is iron depleted

increased pancreas iron level ( J:215585 )

• progressive and marked iron accumulation in pancreatic tissue

• iron accumulates preferentially in the exocrine pancreas, and not in islets of Langerhans

decreased spleen iron level ( J:215585 )

• decrease in splenic iron levels at 8 and 24 weeks of age

• selective iron depletion is seen within iron-recycling macrophages of the red pulp

increased circulating iron level ( J:215585 )

increased brain iron level ( J:215585 )

• accumulation of iron in the brain is seen in the choroid plexus

increased kidney iron level ( J:215585 )

• iron in kidney accumulates predominantly in the renal medulla

increased liver iron level ( J:215585 )

• increase in hepatic iron levels, with preferential iron deposition in the pericentral areas of the liver lobules

• iron accumulates exclusively in hepatocytes

hemochromatosis ( J:215585 )

hematopoietic system

increased erythrocyte cell number ( J:215585 )

increased hematocrit ( J:215585 )

increased hemoglobin content ( J:215585 )

increased mean corpuscular volume ( J:215585 )

decreased spleen iron level ( J:215585 )

• decrease in splenic iron levels at 8 and 24 weeks of age

• selective iron depletion is seen within iron-recycling macrophages of the red pulp

endocrine/exocrine glands

abnormal pancreas morphology ( J:215585 )

• pancreas is dark brown

abnormal pancreatic acinar cell morphology ( J:215585 )

• degeneration of the pancreatic acini starting at 21 weeks of age and worsening thereafter, with severe degeneration at 7 months

increased pancreas iron level ( J:215585 )

• progressive and marked iron accumulation in pancreatic tissue

• iron accumulates preferentially in the exocrine pancreas, and not in islets of Langerhans

growth/size/body

cachexia ( J:215585 )

• wasting is seen at 27 weeks of age

• death is preceded by a sudden and large loss of body weight, with mice humping the back and showing signs of sickness

• mice fed an iron-free diet show prevention of body weight loss and restored survival

• mice fed a chow supplemented with Pancrex, a compound used in pancreatic enzyme replacement therapy, partially reverses weight loss and improves survival

digestive/alimentary system

abnormal pancreatic acinar cell morphology ( J:215585 )

• degeneration of the pancreatic acini starting at 21 weeks of age and worsening thereafter, with severe degeneration at 7 months

decreased intestinal iron level ( J:215585 )

• intestinal epithelium is iron depleted

cellular

oxidative stress ( J:215585 )

• iron accumulation in the pancreas triggers oxidative stress

immune system

decreased spleen iron level ( J:215585 )

• decrease in splenic iron levels at 8 and 24 weeks of age

• selective iron depletion is seen within iron-recycling macrophages of the red pulp

liver/biliary system

abnormal liver morphology ( J:215585 )

• liver is dark brown

increased liver iron level ( J:215585 )

• increase in hepatic iron levels, with preferential iron deposition in the pericentral areas of the liver lobules

• iron accumulates exclusively in hepatocytes

abnormal liver physiology ( J:215585 )

• increase in thiobarbituric acid reactive substances, indicating lipid peroxidation in the liver

• however, no histological evidence of liver damage

cardiovascular system

increased heart iron level ( J:215585 )

• iron accumulates in the heart, mainly in vascular smooth muscle cells

nervous system

increased brain iron level ( J:215585 )

• accumulation of iron in the brain is seen in the choroid plexus

renal/urinary system

increased kidney iron level ( J:215585 )

• iron in kidney accumulates predominantly in the renal medulla

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hemochromatosis type 4		DOID:0111028	OMIM:606069	J:215585