Tracking progressive pathological and functional decline in the rTg4510 mouse model of tauopathy

Table 1 Summary of behavioural and pathological endpoints investigated in the two cohorts of male rTg4510 mice

Cohort 1					12-15 months
Behaviour: spontaneous Y-maze continuous alternation, locomotor activity, Rotarod, aversive Y-maze spatial reference memory, rewarded T-maze alternation, Y-maze spatial novelty preference and rewarded Y-maze visual discrimination.					CC₍₉₎ WW₍₉₎
					↓
Pathology: immunohistochemistry					Perfused
Cohort 2	4 months	6 months	8 months	10 months	12 months
Locomotor activity	CC₍₉₃₎ WW₍₃₀₎	CC-d₍₃₇₎ CC₍₃₈₎ WW₍₁₉₎	CC-d₍₃₆₎ CC₍₃₇₎ WW₍₁₉₎	CC-d₍₁₉₎ CC₍₁₈₎ WW₍₉₎	CC-d₍₁₉₎ CC₍₁₈₎ WW₍₉₎
Rewarded T-maze alternation	CC₍₉₃₎ WW₍₃₀₎	CC-d₍₃₇₎ CC₍₃₈₎ WW₍₁₉₎	CC-d₍₃₆₎ CC₍₃₇₎ WW₍₁₉₎	CC-d₍₁₉₎ CC₍₁₈₎ WW₍₉₎	CC-d₍₁₉₎ CC₍₁₈₎ WW₍₉₎
	↓		↓		↓
Y-maze spatial novelty preference	CC₍₁₆₎ WW₍₁₁₎		CC-d₍₁₇₎ CC₍₁₈₎ WW₍₁₀₎		CC-d₍₁₉₎ CC₍₁₈₎ WW₍₁₀₎
Aversive Y-maze spatial reference memory	CC₍₁₆₎ WW₍₁₁₎		CC-d₍₁₇₎ CC₍₁₈₎ WW₍₁₀₎		CC-d₍₁₉₎ CC₍₁₈₎ WW₍₁₀₎
	↓		↓		↓
Immunohistochemistry and RT-qPCR	Perfused		Perfused		Perfused

12-month-old male rTg4510 mice from the first cohort were tested in seven behavioural assays, as ordered in the table, and then perfused for immunohistochemical assessment of tau pathology
Male mice from cohort 2 were tested from 4 to 12 months in the four pre-defined assays. Following behavioural testing in locomotor activity and T-maze alternation at 4 months, CC animals were split into two treatment groups: doxycycline (CC-d) and non-doxycycline (CC) and tested longitudinally every other month in these two assays until 12 months. At 4, 8, and 12 months, subsets of animals were tested in the Y-maze spatial reference memory and novelty preference assays after which they were all perfused for immunohistochemistry and RT-qPCR analysis
Arrows indicate animals removed from the longitudinal study and undergoing further behavioural testing and perfusion
_(n) = number of mice per group at time point
CC non-doxycycline treated bi-transgenic rTg4510, CC-d doxycycline-treated bi-transgenic rTg4510, RT-qPCR reverse transcription quantitative polymerase chain reaction, WW wild-type rTg4510

ISSN: 1758-9193