Fig. 1. Guinea pig neurological examination. Numbers in parentheses indicate the score assigned to each animal tested depending on the severity of each neurological feature. Scores are circled for each animal in the column on the right, and totalled where indicated.

Fig. 2. Neurological examination score. Test items 1–27, inclusive (see Fig. 1). Scores for each animal were averaged for each time period indicated. Data shown is the mean score for each group of animals at each time period, ±1S.E.M. “*” indicates significantly higher test scores for α-mannosidosis guinea pigs (p < 0.01 for all comparisons in these tests).

Fig. 3. Hind limb stride length and width of guinea pigs at 2 and 3 months of age. Graphs show the mean of stride length (A) or width (B), ±1S.E.M. “*” indicates statistical significance, “ns” indicates no statistical significance.

Fig. 4. Morris water maze. Figure shows acquisition and reversal phase seek times for 2 month old (A) or 3 month old (B) guinea pigs. Data shown is the mean seek time ±1S.E.M. of four trials performed per animal, for each phenotype group, on each day. Maximum duration of each trial was 45 s, after which time the animal was guided to the platform. Failed trials were defined as when the animal did not find the platform during this period. “ns” indicates no statistical significance. (E and F) Shows the mean time spent during the probe phase searching for the platform in each quadrant, for each group at 2 and 3 months, respectively, ±1S.E.M. “Q4” is the target quadrant, containing the platform. “Q1, Q2 and Q3” was the mean time spent in quadrants 1, 2 and 3. Statistical analysis was a t-test performed between the times spent in target quadrant vs. time spent in non-target quadrants, for each group. “*” Indicates statistical significance, “ns” indicates no statistical significance.

Fig. 5. Somatosensory evoked responses. The arrow denotes the voltage stimulus applied to the hindlimb and the resulting somatosensory evoked response trace typically obtained for normal and α-mannosidosis guinea pigs (A). The first major peak (P1), is indicated by the solid or dashed line. (B) Shows the time taken between the stimulus and P1 (P1 latency), calculated in milliseconds, for normal and α-mannosidosis guinea pigs at various ages. Connected data points indicate repeated testing of individual animals.

Fig. 6. Auditory brainstem evoked responses. Typical auditory brainstem evoked response recordings at various acoustic signal intensities in normal (A) and α-mannosidosis (B) guinea pigs. Arrow denotes timing of acoustic stimulus. Asterisks denote the threshold hearing responses for both examples. (C) Shows the minimum threshold of acoustic intensity required to induce a measurable brainstem evoked response, in normal and α-mannosidosis guinea pigs at various ages. Connected data points indicate repeated testing of individual animals.

Fig. 7. Timeline of progression of α-mannosidosis pathology in guinea pigs. Pathological features observed are indicated at various ages throughout the testing period.