COLOBOMA HYPERACTIVE MUTANT EXHIBITS DELAYED NEUROBEHAVIORAL DEVELOPMENTAL MILESTONES

The coloboma mutation (Cm) is a neutron-irradiation induced gene delet ion located on the distal portion of mouse chromosome 2. This deletion region includes a gene encoding the synaptic vesicle docking fusion p rotein, synaptosomal-associated protein of 25 kDa (SNAP-25). The resul ting mutation is semi-dominant with heterozygote mice exhibiting a tri ad of phenotypic abnormalities that comprise profound spontaneous hype ractivity, head bobbing and a prominent eye dysmorphology. Because the expression pattern of two SNAP-25 isoforms begins to change during th e first postnatal week, neurobehavioral developmental milestones were examined in order to determine if the expression of the coloboma behav ioral phenotype could be detected during this period of postnatal deve lopment. The early classification of coloboma mutant offspring may hel p to further describe the penetrance of this mutation as well as the c ontribution of developmental changes to the adult behavioral phenotype . The coloboma mutation resulted in delays in some tests of complex mo tor skills including righting reflex and bar holding. In addition, col oboma mutants were characterized by body weight differences (first app earance day 7) and hyperreactivity to touch (day 11) and head bobbing (day 14). These data demonstrate disruptions in the time course of att aining developmental milestones in coloboma mutants and provide furthe r evidence supporting the hypotheses that alterations in Snap gene exp ression are associated with functional behavioral consequences in deve loping offspring.