Kumar1: Reduced complexity cross between C57BL/6J and C57BL/6N substrains for cocaine response, open field and circadian behaviors (2014)

References   (chronological)

1.   Shimomura K, Low-Zeddies SS, King DP, Steeves TD, Whiteley A, Kushla J, Zemenides PD, Lin A, Vitaterna MH, Churchill GA, Takahashi JS. Genome-wide epistatic interaction analysis reveals complex genetic determinants of circadian behavior in mice. Genome Res. 2001 Jun;11(6):959-80.   PubMed 11381025  

2.   Kumar V, Kim K, Joseph C, Thomas LC, Hong H, Takahashi JS. Second-generation high-throughput forward genetic screen in mice to isolate subtle behavioral mutants. Proc Natl Acad Sci U S A. 2011 Sep 13;108 Suppl 3:15557-64. doi: 10.1073/pnas.1107726108. Epub 2011 Sep 6.   PubMed 21896739     FullText

3.   Kumar V, Kim K, Joseph C, Kourrich S, Yoo SH, Huang HC, Vitaterna MH, de Villena FP, Churchill G, Bonci A, Takahashi JS. C57BL/6N mutation in Cytoplasmic FMRP interacting protein 2 regulates cocaine response. Science. 2013 Dec 20;342(6165):1508-12. doi: 10.1126/science.1245503.   PubMed 24357318  


       
The inbred mouse C57BL/6J is the reference strain for genome sequence and for most behavioral and physiological phenotypes. However, the International Knockout Mouse Consortium uses an embryonic stem cell line derived from a related C57BL/6N substrain. We found that C57BL/6N has a lower acute and sensitized response to cocaine and methamphetamine. We mapped a single causative locus and identified a nonsynonymous mutation of serine to phenylalanine (S968F) in Cytoplasmic FMRP interacting protein 2 (Cyfip2) as the causative variant. The S968F mutation destabilizes CYFIP2, and deletion of the C57BL/6N mutant allele leads to acute and sensitized cocaine-response phenotypes. We propose that CYFIP2 is a key regulator of cocaine response in mammals and present a framework to use mouse substrains to identify previously unknown genes and alleles regulating behavior.

Note on studied population: C57BL/6J x C57BL/6N reduced complexity cross.

Procedures conducted:
• study archive  Open field test. Locomotor, anxiety-related, circadian behavior. Baseline and after cocaine i.p.

Kumar1 downloads
QTL projects have several available downloads.
Use the QTL Data Downloads button near the bottom of this page.
Investigators Vivek Kumar       The Jackson Laboratory,  Bar Harbor, ME
Participants Kim K, Joseph C, Kourrich S, Yoo SH, Huang HC, Vitaterna MH, de Villena FP, Churchill G, Bonci A, Takahashi JS
ContactVivek Kumar     vivek.kumar@jax.org
Affiliated CenterQTL Archive
AcknowledgementsWe thank A. Khan and W. Khan for genotyping help; A. M. Wissman, J. Gibson, and K. Huber for help with diolistics; C. Olker for behavioral testing; C. Cowan for advice on sensitization; M. Strobel for C57BL/6 substrain DNA; S. Padrick, B. Chen, and M. Rosen for WRC reagents and advice; T. Keane (Sanger Centre) for access to sequencing data; N. Kumar and I. Kornblum for technical help; and O. Hermanson and P. Lowrey for advice on manuscript. V.K. was funded through National Research Service Award F32DA024556 from NIDA. NIH grant U01MH61915 funded J.S.T. J.S.T. is an Investigator and S.H.Y. and V.K. were associates in the Howard Hughes Medical Institute.
Project type QTL Archive data set
MPD identifiersKumar1     MPD:290
Data changelog No updates/corrections.       Initial release date: 07/2014.
QTL data set parameters:
Progenitor strains C57BL/6J     C57BL/6NJ    
Cross typeF2 intercross
Population size 113 ♀     131 ♂
Age10-14wks


Measured phenotypes:       To access these data use the QTL Data Downloads button at bottom of page.



Project / data set:   Kumar1     a.k.a. Kumar_2014
Excel file:   Kumar2014_Data_Description.xlsx
CSV file:   Kumar2014_Data.csv
QC plots, figures, etc.:   QCReport_Kumar2014.pdf