Genetic models

Several genetic manipulations have been used to study the pathophysiology, etiology, and pathogenesis of PD.68 Mice with altered DA function can be created by knocking out enzymes involved in DA formation, including tyrosine hydroxylase (TH) catabolic enzymes (monoamine oxidase (MAO), catechol O-methyltransferase (COMT)), DAT, VMAT, or altering DA receptor expression. The findings from these mice are that, unless a marked alteration occurs in striatal DA levels or postsynaptic neurotransmission, no gross abnormalities can be observed.

The identification of genes linked to PD spurred the development of both vertebrate and invertebrate animal models of the disease via either knockout or overexpression strategies. a-Synuclein knockouts show no DA neuron loss or abnormal motor behavior, but do exhibit a subtle alteration of DA receptors in the striatum and altered responses to amphetamine. Transgenic wild-type and mutant (A53T, A30P) a-synuclein mice display neuropathological and behavioral features of PD; however, no one vertebrate model encompasses all disease features.68 Some models show striatal DA deficits accompanied by motor abnormality while others show motor abnormality without deficits in DA content but Lewy body-like pathology. The only model that displays all features of PD is in Drosophila, where there is a loss of DA neurons, cytoplasmic inclusion formation, a DA deficit, and associated motor dysfunction. The only confound is that these features occur with overexpression of either wild-type or mutant a-synuclein, although polymorphisms in the a-synuclein gene promoter as well as genomic multiplication of the a-synuclein locus have been linked in PD patients; thus there is a disease basis for overexpression of the normal protein as perhaps causing the associated dysfunction.

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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