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 Austria offers an extensive CRO service to test your compounds in a frequently used ASD mouse model.
The BTBR T+ tf/J mouse model is a suitable model not only for ASD but also for any other disorder characterized by social deficits.
BTBR T+ tf/J mice are commercially available and 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. Recently 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).
BTBR T+ tf/J mice are an inbred strain completely missing the corpus callosum. Animals present a severely reduced hippocampal commissure. Behavioral analyses of BTBR T+ tf/J mice for motor deficits reveals highly significant reduced motor performance in the wire suspension test (Fig.1A) and nest building test (data not shown). Analysis of the autogrooming behavior shows that the number of grooming bouts are not altered between BTBR T+ tf/J and C57BL/6 mice, but that the mean duration of grooming bouts significantly increased in BTBR T+ tf/J mice (Fig.1B).
Figure 1: Wire suspension time and autogrooming in BTBR T+ tf/J mice. Cut off time of the wire suspension test was 60 seconds and mean duration of grooming bouts is shown of 2 months old animals compared to C57BL/6 mice. BTBR: N = 15; ntg: N = 14 (males only). Statistical analyses by one sample t-test or t-test.
Furthermore, BTBR T+ tf/J mice present with an altered anxiety related behavior that was analyzed with the elevated plus maze test (Fig.2A). Analysis of BTBR T+ tf/J mice for cognitive deficits showed a significantly increased number of wrong choices in the two choice swim test suggesting, that animals have spatial learning deficits (Fig.2B).
Figure 2: Anxiety and cognition of BTBR T+ tf/J mice. Time animals spent in the open arms of the elevated plus maze test and number of wrong choices in the two choice swim test in percent are shown of 2 months old animals compared to C57BL/6 mice. BTBR: N = 15; ntg: N = 14 (males only). Statistical analyses by t-test or 2-way-ANOVA.
Additionally, BTBR T+ tf/J mice were analyzed in the social interaction test, showing, that mice have severe social approach (Fig.3A) and social recognition (Fig.3B) deficits.
Figure 3: 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 and time animals spent sniffing on a familiar or unfamiliar mouse as measure of social recognition in 2 months old animals compared to C57BL/6 mice in the social interaction test. BTBR: N = 15; ntg: N = 14 (males only). Statistical analyses by t-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 social behavior and interaction, exploration, anxiety and cognitive deficits, and are thus a valuable model for ASD research.
QPS Austria 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.