Tg8 mice
Genetically Engineered Lacking the MAO-A Gene
Tg8 mice were genetically engineered out of embryos of C3H mice(which served as the control for this experiment). Their DNA was spliced to exclude exons 2 and 3 of the MAO-A gene. This causes all MAO-A produced by Tg8 to be catalyically inactive because the binding site for cofactor FAD(necessary for catalytic activity) is encoded by exon 2. As a result, Tg8 mice had zero activity for MAO-A and normal activity for MAO-B.
Markedly different results were obtained for juvenile and adult Tg8 mice. Abnormal behavior for pups included:
 frantic running, falling, and jumping
| | digging or hiding in response to moderate sound or movement
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| violent shaking and jumping during sleep
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| hunched posture, and other abnormal postures
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Out of all of these behaviors, only the abnormal postures could be replicated through administration of MAO-A inhibitors to normal C3H mice, even if dosages had begun at birth. Many of the Tg8 pups symptoms could be reduced by a seratonin synthesis inhibitor, suggesting that the abnormal behaviors are a result of excess seratonin.
The abnormal behaviors of Tg8 adult mice included:
| attacked intruders quicker than C3H mice(C3H mice investigated, while Tg8
mice assumed a aggressive posture after first olfactory stimulus)
| | showed wounds from offensive aggressive behavior during weening
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| abnormal mating (Tg8 courtship of an unreceptive female was interrupted by
episodes of grasping)
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| some evidence of minor cognitive deficits
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In addition, when given an MAO-B inhibitor, pups were relatively unaffected, while adult mice behaviors were heavily disrupted. The adults had difficultly in social interactions, feeding, and grooming, because of restlessness and attention deficit. In the mouse brain, MAO-B activity increases with age, while MAO-A activity remains fairly constant throughout life. This is reflected in data which shows that extremely high levels of seratonin in Tg8 pups slowly return to normal with age. Perhaps this indicates that MAO-B is able to pick up some of the slack in breaking down seratonin and catecholamines when MAO-A activity is extremely deficient.
However, the fact remain that the adult mice have several behavioral problems, although they are reduced from the juvenille symptoms. This could be the result of either sructural alterations or persisting monoamine metabolism problems. Structural alterations were found on some regions of the cerebral cortex of adult Tg8 mice, including the somatosensory cortex. Further experiments are needed to determine which is the case.
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