BTBR T+ tf/J Mouse Model
The cause of Autism Spectrum Disorder (ASD) as a complex developmental disorder with highly varying degrees is still under investigation. Research suggests that multiple factors, such as genetic vulnerability and environmental factors are involved in the development of the disorder. QPS Neuropharmacology offers an extensive CRO service to test your compounds in a frequently used ASD mouse model.
BTBR T+ tf/J mice are an inbred strain presenting a severely reduced hippocampal commissure and completely missing the corpus callosum. Mice are the most widely used model for ASD research and related test substance analyses. Various compounds of different classes were positively tested for their efficacy in the BTBR T+ tf/J model. Published examples are the acetylcholinesterase inhibitor donepezil (Karvat & Kimchi, 2013), the noradrenergic reuptake inhibitor atomoxetine (Stapley et al., 2013) and the partial glycineB site agonist D-cycloserine, targeting the NMDA receptor (Burket et al., 2013).
Analysis of the autogrooming behavior shows that the total grooming time is significantly increased in BTBR T+ tf/J mice (Fig. 1)
Figure 1: Autogrooming in BTBR T+ tf/J mice. Total grooming time in seconds of 2 month old animals compared to C57BL/6 mice. BTBR: n = 15; ntg: n = 14 (males only). Mean + SEM Unpaired t-test; **p<0.01.
Additionally, BTBR T+ tf/J mice were analyzed in the social interaction test, showing that mice have severe deficits in social approach (Fig. 2) .
Figure 2: Social behavior of BTBR T+ tf/J mice. Time animals spent sniffing on an unfamiliar mouse or an empty cup as measure of social approach in 2 month old animals compared to C57BL/6 mice in the social interaction test. BTBR: n = 15; ntg: n = 14 (males only). Two-way ANOVA with Bonferroni´s post hoc test.
Our results and that of others (McFarlane et al., 2008; Scattani et al., 2013) show that BTBR T+ tf/J mice display the most common symptoms of ASD, such as repetitive behavior and social deficits and are thus a valuable model for ASD research.
QPS Neuropharmacology offers a custom tailored study design for this model and we are flexible to accommodate to your special interest. We are also happy to advice you and propose study designs. A typical turnaround time from agreement to the study plan to the final report is about 4 months. Animals will be purchased right after your order. Animals of all age groups are typically available without any delay. BTBR T+ tf/J mice show relevant features of ASD already at young age. This allows for extraordinarily fast turn-around times. Furthermore, C57BL/6 mice are available as control animals needed for proper study design.
We would be happy to test your compounds in our BTBR T+ tf/J inbred mouse model! The most common readouts are:
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As with all other in vivo models we are also ready to provide samples (brain tissue, CSF etc.) from these animals for analyses in your laboratory.
We are happy to receive your inquiry.
Stapley NW, Guariglia SR, Chadman KK. Cued and contextual fear conditioning in BTBR mice is improved with training or atomoxetine. Neurosci Lett. 2013 Aug 9;549:120-4. doi: 10.1016/j.neulet.2013.06.032. Epub 2013 Jul 1.
Burket JA, Benson AD, Tang AH, Deutsch SI. D-Cycloserine improves sociability in the BTBR T+ Itpr3tf/J mouse model of autism spectrum disorders with altered Ras/Raf/ERK1/2 signaling. Brain Res Bull. 2013 Jul;96:62-70. doi: 10.1016/j.brainresbull.2013.05.003. Epub 2013 May 15.
Scattoni ML, Martire A, Cartocci G, Ferrante A, Ricceri L. Reduced social interaction, behavioural flexibility and BDNF signalling in the BTBR T+ tf/J strain, a mouse model of autism. Behav Brain Res. 2013 Aug 15;251:35-40. doi: 10.1016/j.bbr.2012.12.028. Epub 2012 Dec 25.