Phenotypes Associated with This Genotype

Genotype
MGI:5775427

• Allelic Composition: Cox10^tm1Ctm/Cox10^tm1Ctm; Slc6a3^{tm1.1(cre)Bkmn}/?
• Genetic Background: B6.Cg-Cox10^tm1Ctm Slc6a3^{tm1.1(cre)Bkmn}

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

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:231810 )

• mice exhibit a decline in motor activity and coordination by 2 months of age, maximum decline is reached by 4 months of age

impaired coordination ( J:231810 )

• mice are not able to perform the pole test by 2 months of age, however, treatment with high dose L-DOPA (25 mg/kg) or pioglitazone improves performance

• impaired rotarod performance by 2 months of age, however, treatment with high dose L-DOPA (25 mg/kg) or pioglitazone improves performance

• walking time is decreased on rotarod at 4 and 6 months as compared to younger animals

decreased vertical activity ( J:231810 )

• decrease in rearing activity by 2 months of age, maximum decline is reached by 4 months of age

decreased locomotor activity ( J:231810 )

• mice move less during nocturnal cycle and in open field test (distance travelled) as compared to controls; treatment with high dose L-DOPA (25 mg/kg) results in hyperactivity and stereotypic movements

• maximum decline in motor performance is reached at 4 months of age

hematopoietic system

microgliosis ( J:231810 )

increased microglial cell activation ( J:231810 )

• activation of microglial cells in midbrain as detected by Iba1 immunoreactivity

• treatment with pioglitazone for 4 months results in reduction in Iba1 immunoreactivity in midbrain

growth/size/body

decreased body weight ( J:231810 )

• pups are born at a lower body weight than controls and remain at a lower weight throughout life

• administration of pioglitazone increases weight to control levels

immune system

microgliosis ( J:231810 )

increased microglial cell activation ( J:231810 )

• activation of microglial cells in midbrain as detected by Iba1 immunoreactivity

• treatment with pioglitazone for 4 months results in reduction in Iba1 immunoreactivity in midbrain

abnormal chemokine secretion ( J:231810 )

• CXCL10 and CCL2 are increased in striatum

• in midbrain, levels of IL6, IL10, CXCL10 and CCL2 trend upward, but do not reach significance

increased interleukin-1 beta secretion ( J:231810 )

• increase in IL1B in midbrain in 2 month old mice

• IL1B is slightly increased in striatum but does not reach significance

homeostasis/metabolism

decreased dopamine level ( J:231810 )

• decrease in dopamine and dopamine metabolites (to a lesser extent) in striatum by 2 months of age as compared to controls

• dopamine depletion continues through out life but does not worsen

nervous system

microgliosis ( J:231810 )

increased microglial cell activation ( J:231810 )

• activation of microglial cells in midbrain as detected by Iba1 immunoreactivity

• treatment with pioglitazone for 4 months results in reduction in Iba1 immunoreactivity in midbrain

decreased dopaminergic neuron number ( J:231810 )

loss of dopaminergic neurons ( J:231810 )

• substantial loss of dopaminergic cell bodies in the substantial nigra as measured by reduction of tyrosine hydroxylase (TH) and dopamine transporter (DAT) content

• widespread axonal degeneration in striatum

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease		DOID:14330	OMIM:PS168600	J:231810