• age-related impairment in conditioned avoidance tests, seen at 10 months of age, but not at 4 months of age

• impairment in watermaze test of spatial learning, both at 4 and 10 months of age

• significantly reduced grip strength

• decreased locomotor activity

• reactive gliosis was observed throughout the cortical layers of the neocortex and extensive astrogliosis was seen in the CA1 region of the hippocampus, however did not observe neuronal cell damage

• reactive astrocytosis in many brain areas, but predominantly in the cortex and hippocampus at 14 weeks of age

• the branching of dendrites of both cortical and hippocampal neurons was much less extensive, however did not show any loss of cells in the cortex or the hippocampus

• impairment of ability of high frequency stimuli to induce LTP which correlated with extent of gliosis in stratum radiatum

• body weight was 15-20% less at all ages compared with that of controls

• mutants start to die at 50 days of age

• mutants exhibit severe weight loss, with weight at 3 weeks of age lower than seen in single homozygous App mice, but then increases so that by 12 weeks of age, loss of body weight is similar to single Npc1 homozygotes

• lower number of surviving Purkinje cells in cerebellar lobes VIII and X

• mutants exhibit a greater increase in astrocytosis and microglia activation than in single Npc1 homozygotes

• mutants exhibit demyelination in the white matter

• mutants exhibit an exacerbated motor coordination deficit than seen in single Npc1 homozygotes

• mutants exhibit a greater vesicular accumulation of and wider distribution of cholesterol in the cerebellum, the motor cortex, the hippocampus and dentate gyrus than single Npc1 homozygotes

• although born in Mendelian ratios, few mice survive to adulthood

• neuromuscular junction exhibit mislocalization of choline transporters and reduced synaptophysin staining compared with wild-type mice

• although born in Mendelian ratios, no mice survive to weaning

• the cerebellum volume is not as small as in Dab1^tm1Bwh homozygotes

• the cerebellum volume is not as small as in Dab1^tm1Bwh homozygotes

• incomplete penetrance, 80% of mice die within one week of birth

• lethality is not due to cardiopulmonary function as the heart and lungs appeared normal

• most pups have little or no milk in stomach, however no lesions in the face, palate, esophagous, stomach, intestine, or colon were seen and cranial nerves implicated in feeding appeared normal

• by 12-36 hours after birth, double homozygous mice appear weaker, however mice exhibit normal muscle histology, abundant lower motor neurons in the ventral horn of spinal cords, and normal neuromuscular transmission

• survivors lag behind in growth and are 20-30% smaller, even into adulthood, compared to controls

• no abnormalities in ovaries and testis, indicating that physiological or behavioral correlates, rather than anatomical aspects, are responsible for decrease in fertility

• become pale by 12-36 hours after birth