BEHAVIORAL DIFFERENCES IN A MOUSE MODEL OF BATTEN DISEASE

Juvenile neuronal ceroid lipofuscinosis (JNCL), or Batten disease, is an autosomal recessive human neurodegenerative disease caused by a mutation in the CLN3 gene. Symptoms of Batten disease are first observed around five years of age and include progressive visual, motor, and cognitive deterioration and seizures that lead to premature death during the third decade of life. Mouse models with differing mutations in Cln3 (the mouse homologue of CLN3) have been used to study Batten disease. In this study, behavioral performances of Cln3 knock-in mice (KI) were compared to wild-type controls (WT) to assess cognitive or locomotor differences prior to the onset of serious Batten disease symptoms. Motor and cognitive functioning of the mice were assessed using force-plate actometers and operant chambers, respectively. There were no differences between KI and WT mice in overall locomotion or stationary movement, but KI mice engaged in more active bouts of locomotion (20 or more centimeters traveled in 2.56 seconds) than WT controls. In addition, KI mice consistently made fewer operant responses and earned fewer rewards than controls. Together, these results show that Cln3 KI mice have a distinct behavioral phenotype prior to developing debilitating Batten disease-like symptoms. Defining a behavioral profile for Cln3 KI mice may help determine the effectiveness of future treatments and therapies for this disease. Moreover, studies comparing the Cln3 KI mice to other current Batten disease models may provide insight into the diagnosis, treatment, and understanding of disease progression.

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