Phenotypes associated with this allele

• Allele Symbol: Tg(PGK1-FTL*)#Sle
• Allele Name: transgene insertion, Sonia Levi
• Allele ID: MGI:5700531
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
tg1	Tg(PGK1-FTL*)#Sle/0	B6J.FVB-Tg(PGK1-FTL*)#Sle	MGI:5700536
tg2	Tg(PGK1-FTL*)#Sle/0	involves: FVB/N	MGI:5700532

Genotype
MGI:5700536

tg1

• 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

Genotype
MGI:5700532

tg2

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

cellular

oxidative stress ( J:227451 )

• mice show a higher level of carbonylated proteins in the brain at 6 months and show a 2-fold increase at 12 months, indicating oxidative damage

behavior/neurological

behavior/neurological phenotype ( J:226967 )

N • Background Sensitivity: mice on the FVB/N background behave similarly to wild-type mice in behavioral tests and no locomotor differences are seen up to 2 years of age unlike mice on a congenic C57BL/6J background which have impaired coordination

abnormal behavioral response to xenobiotic ( J:226967 )

• mice treated with the herbicides Paraquat and Maneb to induce neurodegeneration show an increase in locomotor, rearing and exploratory activity compared to controls

homeostasis/metabolism

abnormal iron homeostasis ( J:227451 )

• ferritin iron/ferritin protein ratio is lower in the brain, indicating a reduced capacity of the ferritin to incorporate iron

increased brain iron level ( J:227451 )

• mice show increased iron and ferritin accumulation in the brain at 12 and 22 months of age

• Background Sensitivity: iron and ferritin accumulation is higher on the FVB/N background than on a congenic C57BL/6J background

nervous system

increased brain iron level ( J:227451 )

• mice show increased iron and ferritin accumulation in the brain at 12 and 22 months of age

• Background Sensitivity: iron and ferritin accumulation is higher on the FVB/N background than on a congenic C57BL/6J background

neuronal intranuclear inclusions ( J:227451 )

• mice show the presence of aggregates of human ferritin inside neurons at 18 and 22 months of age