Phenotypes Associated with This Genotype

Genotype
MGI:5441517

• Allelic Composition: Gt(ROSA)26Sor^{tm1.1(CAG-COX8A/Dendra2)Dcc}/Gt(ROSA)26Sor⁺; Mfn2^tm3Dcc/Mfn2^tm3Dcc; Slc6a3^{tm1.1(cre)Bkmn}/Slc6a3⁺
• Genetic Background: involves: 129 * 129S6/SvEvTac * C57BL/6J * SJL/J

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

mortality/aging

premature death ( J:188347 )

• mutants die around 6-7 weeks of age due to malnutrition; this is most likely due to difficulty accessing food and water in normal cages due to a rearing defect

• however, when mutants are supplied with hydrated gel packs and crushed pieces of regular chow, all mutants survive beyond 6 months of age, with a majority surviving past 1 year of age

growth/size/body

decreased body size ( J:188347 )

• mutants are significantly smaller than controls by 5 weeks of age

decreased body weight ( J:188347 )

• mutants do not gain weight after 4 weeks of age

behavior/neurological

hunched posture ( J:188347 )

• mutants are hunched by 5 weeks of age

decreased vertical activity ( J:188347 )

• severe rearing defect as early as 4 weeks of age

• treatment of mutants with L-DOPA alleviates the motor defects

decreased locomotor activity ( J:188347 )

• mutants are hypoactive by 5 weeks of age

• at 4-5 weeks of age, mutants travel only 68% of the distance traveled by wild-type mice and by 8-11 weeks of age, the distance traveled reduces to 34% of wild-type, indicating an age-dependent decline in locomotive activity

bradykinesia ( J:188347 )

• beginning at 4-5 weeks, mutants exhibit progressive bradykinesia

• mutants exhibit a decline in the speed of movement with age compared to controls

• mutants spend twice as much time inactive at 6-7 weeks of age as controls and by 8-11 weeks of age, this increases to 6-fold increase in inactive time

nervous system

abnormal striatum morphology ( J:188347 )

• loss of dopaminergic terminals in the striatum, with a 25% reduction in dopaminergic terminals at 3 weeks of age and 76% reduction by 8-10 weeks

abnormal innervation ( J:188347 )

• mutants exhibit loss of dopaminergic efferents to the striatum, with a 25% reduction in dopaminergic terminals at 3 weeks of age and a 76% reduction by 8-10 weeks of age

• however, projections to the nucleus accumbens and olfactory tubercle are protected and the dopaminergic terminals are moderately preserved at 11-14 weeks

abnormal dopaminergic neuron morphology ( J:188347 )

• dopaminergic neurons remaining have smaller cell bodies and diminished neuronal processes

• dopaminergic neurons exhibit mitochondrial fragmentation and depletion

loss of dopaminergic neurons ( J:188347 )

• retrograde degeneration of substantia nigra pars compacta dopaminergic neurons and to a lesser extent in the mesolimbic pathway

neurodegeneration ( J:188347 )

• progressive, retrograde degeneration of dopaminergic neurons in the nigrostriatal circuit, with neuronal loss first seen at 10-12 weeks, when a 52% decrease in TH-positive neurons is seen

• some degeneration is also seen in the mesolimbic pathway, although a lesser extent than in the nigrostriatal circuit

• degeneration of dopaminergic neurons occurs in a stepwise manner, with initial defects at the axon terminals, followed 1-2 months later by degeneration of the cell bodies

abnormal axonal transport ( J:188347 )

• mutants show decreased mitochondrial transport along nerve processes

cellular

abnormal mitochondrial morphology ( J:188347 )

• dopaminergic neurons exhibit mitochondrial fragmentation and depletion

skeleton

kyphosis ( J:188347 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease		DOID:14330	OMIM:PS168600	J:188347