Mutation-induced loss of APP function causes GABAergic depletion in recessive familial Alzheimer’s disease: analysis of Osaka mutation-knockin mice

Table 2 Phenotypes of OSK-KI mice in comprehensive behavioral test battery

Tests	Hetero-KI	Homo-KI
Tests	(vs. Non-KI)	(vs. Non-KI)	(vs. Hetero-KI)
Somatic parameters
Body weight	─	─	↓¹
Body temperature	─	─	─
Grip strength	─	─	─
Wire-hanging time	─	─	─
Light/dark transition test
Anxiety	─	─	↓²
Open field
Exploratory locomotion	─	─	─
Elevated plus maze
Anxiety	─	─	─
Rotarod
Motor coordination	↓³	↓³	─
Hot plate
Pain sensitivity	─	─	─
Social interaction test (novel environment)	─	─	─
Social interaction test (Crawley’s version)	─	─	─
Startle Response/Prepulse inhibition
Sensorimotor gating	↓⁴	─	↑⁴
Porsolt forced swim
Immobility time (behavioral despair)	─	─	─
Barns maze
Spatial memory	─	↑⁵	─
Eight-arm radial maze
Working memory	─	↑⁶	─
T-maze forced alternation
Working memory	─	─	─
Gait analysis
Gait ataxia	─	─	─
Fear conditioning
Contextual fear memory	─	─	─
Tail suspension
Immobility time (behavioral despair)	─	─	─
Social interaction test (24-h homecage monitoring)	─	↓⁷	─

Comprehensive behavioral test battery was performed on 8-month-old male mice as described previously [10]. The numbers of mice used in each test were n = 15–17 for non-KI, n = 16–20 for hetero-KI, and n = 12–16 for homo-KI except for the social interaction tests (novel environment and 24-h homecage monitoring) in which n = 7–9 for non-KI, n = 8–10 for hetero-KI, and n = 6–8 for homo-KI. ─, no significant difference was detected. ↓¹, body weight of homo-KI was slightly but significantly (p < 0.05) lower than that of hetero-KI. ↓², distance traveled in dark of homo-KI was slightly but significantly (p < 0.05) lower than that of hetero-KI. ↓³, latency to fall of hetero-KI was significantly (p < 0.05) lower than that of non-KI; latency to fall of homo-KI was also lower than that of non-KI, but the difference was not significant. ↓⁴ and ↑⁴, prepulse inhibition of hetero-KI was lower than those of non-KI and homo-KI, but the differences were not significant. ↑⁵, error to 1st of homo-KI was slightly but significantly (p < 0.05) lower (i.e. improved) than that of non-KI. ↑⁶, different arm choices in first 8 entries of homo-KI was slightly but significantly (p < 0.05) higher (i.e. improved) than that of non-KI. ↓⁷, activity level in dark of homo-KI was significantly (p < 0.05) lower than that of non-KI

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