This strain is used in studies of autism because it exhibits several symptoms of autism including reduced social interactions, impaired play, unusual vocalizations as compared to other inbred strains. BTBR mice exhibit a 100% absence of the corpus callosum and a severely reduced hippocampal commissure.Read More +
BTBR mice exhibit a 100% absence of the corpus callosum and a severely reduced hippocampal commissure (Wahlsten D, 2003 Brain Res). This strain exhibits several symptoms of autism including reduced social interactions, impaired play, low exploratory behavior, unusual vocalizations and high anxiety as compared to other inbred strains (McFarlane HG, 2008, Gen, Brain Behav; Moy SS, 2007, Behav Br Res, Scattoni ML, 2008, PLos). Diet has been found to impact these phenotypes, levels of neuroinflammation, neurogenesis and synaptic function (Currais et al., 2016, Mol Psych).
This inbred strain recognized by its distinctive black and tan coat color and abnormal hair growth pattern and appearance. Specifically, mice homozygous for the spontaneous tufted mutation (Itpr3tf) exhibit alternating waves of hair loss and growth are repeated throughout the life of the mouse, creating a sparse hair appearance (Lyon MF, 1956, J Hered).
In 2019-2020, researchers at The Jackson Laboratory discovered this inbred strain contains the Trem2S148E allele - a naturally occurring variant at position 48351151-48351152 on Chr 17 (rs108080490 and rs107649577; Ensembl GRCm38.p6). This TC to GA transition results in a serine to glutamic acid substitution at amino acid 148 (S148E).
The BTBR T+ Itpr3tf/J strain was derived from the inbred strain BTBR (Black and Tan BRachyury) that carried the mutations at (nonagouti; black and tan), Itpr3tf (inositol 1,4,5-triphosphate receptor 3; tufted), and T (brachyury). The BTBR strain was developed by L.C. Dunn from stock obtained from Dobrovolskaia-Zavadskaia. He brother-sister mated the stock at Columbia University and inserted tufted (Itpr3tf) as a marker around 1956. The stock was continuously inbred in the laboratory of the late Dorothea Bennett from 1962 and then brought by Karen Atrzt in 1974 from the Bennett laboratory to the laboratory of Jean-Louis Guenet at the Institut Pasteur, who sent the strain in 1982 to the McArdle Laboratory at the University of Wisconsin. The T locus had been maintained in the strain as a segregating locus, but had been dropped sometime prior to the acquisition of the current strain by The Jackson Laboratory from Alexandra Shedlovsky and Bill Dove at the McArdle Laboratory in 1994.
|Gene Symbol and Name||Itpr3, inositol 1,4,5-triphosphate receptor 3|
|Strain of Origin||BTBR|
|General Note||This allele was recovered from a Harwell testing stock carrying multiple recessive markers in an undefined background. (J:273)|
|Molecular Note||Complementation mapping was used to demonstrate that this spontaneous mutation was an allele of Itpr3. Sequencing revealed a 12 bp deletion in Exon23 (Chr17: 27238069, Build 38.1) which codes for amino acids 983-986. This mutation arose early in the history of the BTBR strain (in or soon after 1956) and is not found in 18 other strains (129P2/OlaHsd, 129S1/SvImJ, 129S5/SvEvBrd, A/J, AKR/J, BALB/cJ, C3H/HeJ, C57BL/6NJ, CAST/EiJ, CBA/J, DBA/2J, FVB/NJ, LP/J, NOD/ShiLtJ, NZO/HlLtJ, PWK/PhJ, SPRET/EiJ and WSB/EiJ)|
|Allele Synonym(s)||Disc1129S6; Disc1delta6|
|Gene Symbol and Name||Disc1, disrupted in schizophrenia 1|
|Strain of Origin||various|
|General Note||This deletion appears in multiple strains of the 129 superfamily, 101/RI, BTBR T+ tf/J, LP/J, FVB/NJ, SJL/J, SWR/J and DDY/JclSidSeyFrkJ (J:111837, J:195189).|
|Molecular Note||A 25 bp deletion in exon 6 causes a frame shift in the reading frame, resulting in 13 novel amino acids and a premature stop codon in exon 7.|
|Allele Type||Not Applicable (Not Specified)|
|Gene Symbol and Name||Cox7a2l, cytochrome c oxidase subunit 7A2 like|
|Strain of Origin||multiple strains|
|General Note||Querying the sequences of the Sanger Mouse Genomes Project reveals that the short allele with its 6 bp deletion exists in C57BL/6J, C57BL/10J, C57BL/6NJ, C58/J, BALB/cJ, C3H/HeH, 129S5/SvEvBrd, NZW/LacZ, and SEA/GnJ, but the long allele lacking the deletion exists in 129S1/SvImJ, A/J, AKR/J, BTBR T+ Itpr3tf/J, BUB/BnJ, C3H/HeJ, C57BR/cdJ, C57L/J, CAST/EiJ, CBA/J, DBA/1J, DBA/2J, FVB/NJ, I/LnJ, KK/HiJ, LEWES/EiJ, LP/J, MOLF/EiJ, NOD/ShiLtJ, NZB/BlNJ, NZO/HlLtJ, PWK/PhJ, RF/J, SPRET/EiJ, ST/bJ, WSB/EiJ, ZALENDE/EiJ.|
|Molecular Note||This allele encodes the long isoform with 113 amino acids. It is found in 129S2/SvPasCrl, CBA/CaOlaHsd, Hsd:ICR, and NZB/OlaHsd.|
When using the BTBR mouse strain in a publication, please include JAX stock #002282 in your Materials and Methods section.