Phenotypes Associated with This Genotype

Genotype
MGI:5700536

• Allelic Composition: Tg(PGK1-FTL*)#Sle/0
• Genetic Background: B6J.FVB-Tg(PGK1-FTL*)#Sle

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

behavior/neurological

impaired coordination ( J:226967 , J:227451 )

• adult mutants show a lower latency to fall from a beam compared to wild-type mice at 8 months of age; females show an even shorter latency than males (J:226967)

• Background Sensitivity: unlike mice on a FVB/N background which show no behavioral impairments, mice on the congenic C57BL/6J background have impaired coordination (J:226967)

• at 18 months of age, mutants fall from the rotarod earlier than controls (J:227451)

abnormal gait ( J:226967 )

• 18 month old mutants show an abnormal pattern in the fore-base width of their gait

cellular

oxidative stress ( J:227451 )

• mice show higher levels of oxidized proteins, higher levels of protein ubiquitination, higher levels of lipidic peroxidation, and higher levels of DNA oxidation, indicating oxidative damage in the brain

• primary cultures of hippocampal neurons show increased susceptibility to oxidative stress from chronic iron overload and/or after acute hydrogen peroxide exposure

homeostasis/metabolism

decreased circulating ferritin level ( J:227451 )

• serum endogenous ferritin levels are halved

increased brain iron level ( J:226967 , J:227451 )

• iron accumulation beginning at 6 months of age and increases with age (J:226967)

• mice show increased iron and ferritin accumulation in the brain at 12 and 22 months of age (J:227451)

• Background Sensitivity: iron and ferritin accumulation is lower on the congenic C57BL/6J background than on the FVB/N background (J:227451)

nervous system

increased brain iron level ( J:226967 , J:227451 )

• iron accumulation beginning at 6 months of age and increases with age (J:226967)

• mice show increased iron and ferritin accumulation in the brain at 12 and 22 months of age (J:227451)

• Background Sensitivity: iron and ferritin accumulation is lower on the congenic C57BL/6J background than on the FVB/N background (J:227451)

neuronal intranuclear inclusions ( J:226967 )

• presence of ferritin/iron bodies is most tissues, principally in the brain

• ferritin/iron inclusions become detectable at 6 months of age and the number and size of granules increase with age

pigmentation

lipofuscinosis ( J:227451 )

• mice show an increase in the presence of small, membrane bounded and vacuolated, osmophilic bodies in the cytoplasm at 12 months of age, indicative of lipofuscin granules

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neurodegeneration with brain iron accumulation 3		DOID:0110737	OMIM:606159	J:226967