International Meeting for Autism Research (London, May 15-17, 2008): The Development of a PKU Monkey Model to Study the Behavioral Phenotype and Neuropathology of Autism in Non-Human Primates

The Development of a PKU Monkey Model to Study the Behavioral Phenotype and Neuropathology of Autism in Non-Human Primates

Saturday, May 17, 2008
Champagne Terrace/Bordeaux (Novotel London West)
L. A. Martin , Psychology, Azusa Pacific University, Azusa, CA
D. G. Amaral , The M.I.N.D. Institute, UC Davis, Sacramento, CA
Although the etiology of most autism spectrum disorders (ASD) is unknown, it is estimated that between 10-20% of ASD cases are caused by known medical conditions. Included in the list of medical conditions known to cause autism is Phenylketonuria (PKU). PKU is a genetic disorder of metabolism involving the failure to covert phenylalanine to tyrosine resulting in both social and cognitive deficits.
In this study, PKU was simulated through the delivery of a high phenylalanine diet to pregnant rhesus monkeys. These hyperphenylalaninemic monkeys provide a potentially reliable model in which the behavioral phenotype and neuropathology of autism can be explored in non-human primates.
Beginning halfway through their pregnancy, 3 rhesus monkeys were given 1 g/kg body weight of phenylalanine daily until they gave birth. Five pregnant rhesus monkeys were left untreated to serve as controls. An additional group of 4 controls from an unrelated study were also included with the 5 controls in this study. Each infant was raised with their mother, and each mother/infant pair was socialized daily with an adult male and 5 additional mother/infant pairs. The infants were tested in a variety of behavioral paradigms aimed at exploring social and motor deficits in these monkeys. These paradigms included preweaning social group and mother/infant-mother/infant tetrad observations and postweaning social group and familiar and unfamiliar pairings.
Preweaning social group and tetrad observations revealed significant differences in the frequency and duration of social and communicative behavior of hyperphenylalaninemic versus control infants. Postweaning observations of social groups and familiar and unfamiliar pairings did not reveal any significant differences between hyperphenylalaninemic and control groups. 
Hyperphenylalaninemic monkeys provide a promising model to study the behavioral phenotype of autism in non-human primates. Establishing a reliable non-human primate model can lead to detailed studies of the neuropathology of autistic behavior.