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Autism Mouse Models

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SFARI and The Jackson Laboratory are collaborating to increase the availability of autism mouse models to the research community.

Mouse models are essential to advance understanding of the mechanistic basis of autism spectrum disorders, as well as to test potential therapies. There is a growing list of models with good construct validity — meaning that they carry a mutation in a known risk gene — and face validity, or bearing some physical or behavioral resemblance to the human disorder.

Still, there remain significant barriers to the rapid distribution of these resources from individual academic labs. SFARI has made a commitment to establish colonies of the best of these models at The Jackson Laboratory, which will allow any interested researcher to gain access to them in the shortest amount of time possible and at minimal cost.

Click here for more information on the rationale for this initiative and other related mouse projects.

The following mouse lines are either currently or soon to be available from The Jackson Laboratory. We are grateful to the principal investigators whose labs generated these mice for making these valuable resources available to the community. Researchers who are interested in ordering these mice and would like more information should contact Cathleen Lutz at The Jackson Lab (cat.lutz@jax.org).

16p11.2 deletion

Donating investigator/institution: Alea Mills, Ph.D./Cold Spring Harbor Laboratory

Description: These mutant mice possess an engineered deletion spanning approximately 0.39 megabases on mouse chromosome 7, a region that shares conserved synteny with human chromosome 161.

16p11.2 deletion

Donating investigators/institutions: Ricardo Dolmetsch, Ph.D./Stanford University; Jacqueline Crawley, Ph.D./University of California Davis School of Medicine

Description: This line has the syntenic 440 kilobase-pair region on mouse chromosome 7F3 deleted (between and including CORO1A to SPN) and also expresses a membrane-targeted fluorescent reporter gene (mCherry) under the control of the CAG promoter2.

16p11.2 duplication

Donating investigator/institution: Alea Mills, Ph.D./Cold Spring Harbor Laboratory

Description: These mutant mice possess an engineered duplication of approximately 0.39 megabases of mouse chromosome 7, a region that shares conserved synteny with human chromosome 161.

CACNA1C deletion

Donating investigator/institution: Randall Rasmusson, Ph.D./University of Buffalo, The State University of New York

Description: These mutant mice harbor a G406R mutation in exon 8a, as well as an inverted neo cassette3.

CNTNAP2 (CASPR2) deletion

Donating investigator/institution: Elior Peles, Ph.D./Weizmann Institute of Science

Description: CNTNAP2-null mice were generated by a standard gene-targeting approach, resulting in the replacement of its first exon, which includes the translation initiation site and its signal sequence with a neo gene4,5.

SHANK3 deletion

Donating investigator/institution: Joseph Buxbaum, Ph.D./Mount Sinai School of Medicine

Description: These mutant mice harbor a deletion of the SH3/ankyrin domain gene 3 (SHANK3) ankyrin repeat domains (exons 4-9); this deletion prevents full-length SHANK3 expression6.

SHANK3 deletion

Donating investigator/institution: Guoping Feng, Ph.D./Duke University

Description: These mutant mice harbor a deletion of the PDZ domain, which eliminates expression of the ‘A’ and ‘B’ isoformsr.

UBE3a variant 1 overexpression

Donating investigator/institution: Scott Dindot, Ph.D./Texas A&M University

Description: These transgenic mice allow Tet-off/ Tet-on expression of a FLAG-tagged UBE3a splice variant 1 protein, in addition to normal expression of endogenous UBE3a. Funded in collaboration with Dup15q Alliance.

UBE3a variant 2 overexpression

Donating investigator/institution: Scott Dindot, Ph.D./Texas A&M University

Description: These transgenic mice allow Tet-off/ Tet-on expression of a FLAG-tagged UBE3a splice variant 2 protein, in addition to normal expression of endogenous UBE3a. Funded in collaboration with Dup15q Alliance.

UBE3a variant 2, 3 overexpression

Donating investigator/institution: Matthew Anderson, M.D., Ph.D./Beth Israel Deaconess Medical Center, Harvard Medical School

Description: These transgenic mice allow expression of FLAG-tagged UBE3a long isoforms (splice variants 2 and 3, L), in addition to endogenous UBE3a8.

We are in the process of identifying additional lines of mutant mice that hold sufficient promise as models of autism spectrum disorders. As these mice are transferred to The Jackson Lab we will update this page accordingly.

Researchers who are interested in having a particular mutant mouse placed at The Jackson Lab should send a brief description of the mouse and a rationale for its inclusion to mousemodels@simonsfoundation.org.

References:

1. Horev G. et al. Proc. Natl. Acad. Sci. USA 108, 17076-17081 (2011) PubMed

2. Portmann T. et al. Cell Rep. 7, 1077-1092 (2014) PubMed

3. Bader P.L. et al. Proc. Natl. Acad. Sci. USA 108, 15432-15437 (2011) PubMed

4. Poliak S. et al. J. Cell Biol. 162, 1149-1160 (2003) PubMed

5. Peñagarikano O. et al. Cell 147, 235-246 (2011) PubMed

6. Bozdagi O. et al. Mol. Autism 1, 15 (2010) PubMed

7. Peça J. et al. Nature 472, 437-442 (2011) PubMed

8. Smith S.E., et al. Sci Transl Med 3, 103ra197 (2011) PubMed