Phenotypes Associated with This Genotype

Genotype
MGI:4437054

• Allelic Composition: Nr4a2^tm1.1Pcn/Nr4a2^tm1.1Pcn; Slc6a3^tm1(cre)Lrsn/Slc6a3^tm1(cre)Lrsn
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

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

mortality/aging

lethality at weaning, complete penetrance ( J:157098 )

• mice do not survive beyond 3 weeks

• however, leaving pups with mothers improves perinatal survival beyond 3 weeks

nervous system

abnormal dopaminergic neuron morphology ( J:157098 )

• expression of midbrain dopamine neuron markers is lost compared to in wild-type mice

neuron degeneration ( J:157098 )

• mice exhibit a rapid loss of substantia nigra pars compacta cell bodies with only scattered ventral tegmental area neurons remaining compared with wild-type mice

behavior/neurological

decreased vertical activity ( J:157098 )

• at 4 and 14 months

decreased locomotor activity ( J:157098 )

hyperactivity ( J:157098 )

• L-DOPA-treated mice exhibit hyperactivity unlike similarly treated wild-type mice

increased stereotypic behavior ( J:157098 )

• L-DOPA-treated mice exhibit repetitive behaviors (including repetitive gnawing, excessive grooming, and self-injury) unlike similarly treated wild-type mice

homeostasis/metabolism

decreased dopamine level ( J:157098 )

• at P1, striatal dopamine levels are decreased to 14% of wild-type

• at P14, the ratio of homovanillic acid (HVA) to dopamine is increased indicating increased dopamine turnover compared to in wild-type mice

• at P60, striatal dopamine levels are almost completely lost unlike in wild-type mice

• at P60, dopamine levels are more severely decreased in the caudate putamen compared to in the nucleus accumbens

increased serotonin level ( J:157098 )

• serotonin levels in the caudate putamen and nucleus accumbens are increased compared to in wild-type mice

abnormal response/metabolism to endogenous compounds ( J:157098 )

• L-DOPA-treated mice exhibit hyperactivity and repetitive behaviors unlike similarly treated wild-type mice

growth/size/body

decreased body size ( J:157098 )

• at 2 months, mice left with their mothers after weaning are 40% smaller than wild-type mice