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  


     
Kumar1 downloads
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Use the QTL Data Downloads button near the bottom of this page.
Participants Vivek Kumar       The Jackson Laboratory Bar Harbor, ME
With: 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
AffiliationChurchill Group QTL 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.
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.


QTL data set parameters:
Progenitor strains C57BL/6J     C57BL/6NJ    
Cross typeF2 intercross
Population size 113 ♀     131 ♂


Measured phenotypes:       To access these data use the QTL Data Downloads button at bottom of page.
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Data set MPD ID Procedure / Protocol Drug or Challenge Phenotype Measure Panel No. of Strains Sex Age Sample Size (Avg)
Kumar1 29001 open field test cocaine cocaine response over 30 minutes; data are averaged in 5 minute bins and then summed over 30 minutes   [cm x 100]  1sum_5min_avg QTL population both 10-14wks N=122
Kumar1 29002 open field test cocaine cocaine response over 60 minutes; data are averaged in 5 minute bins and then summed over 60 minutes   [cm x 100]  1sum_60min QTL population both 10-14wks N=122
Kumar1 29003 open field test (none) average speed over 30 minutes of baseline   [cm/sec x 100]  1baseline_avg QTL population both 10-14wks N=122
Kumar1 29004 open field test cocaine average speed over 30 minutes after cocaine response   [cm/sec x 100]  130avg QTL population both 10-14wks N=122
Kumar1 29005 open field test cocaine net response–baselineavg subracted from 30avg   [cm/sec x 100]  1resp-baseline QTL population both 10-14wks N=122
Kumar1 29006 open field test (none) circadian period   [hour]  Tau1_(ChiSq) QTL population both 10-14 wks N=122
Kumar1 29007 open field test (none) amplitude  Power_FFT QTL population both 10-14 wks N=122
Kumar1 29008 open field test (none) revolution per minute on wheels   [n]  Avg_Counts QTL population both 10-14 wks N=122
Kumar1 29009 open field test (none) total distance traveled during test   [cm x 100]  T1TotalDist QTL population both 10-14wks N=122
Kumar1 29010 open field test (none) distance traveled in corner   [cm x 100]  T1CornerDist QTL population both 10-14wks N=122
Kumar1 29011 open field test (none) distance traveled in periphery   [cm x 100]  T1PeripheralDist QTL population both 10-14wks N=122
Kumar1 29012 open field test (none) distance traveled in center   [cm x 100]  T1CenterDist QTL population both 10-14wks N=122
Kumar1 29013 open field test (none) percent of distance traveled in corner   [%]  T1PercentCornerDist QTL population both 10-14wks N=122
Kumar1 29014 open field test (none) percent of distance traveled in periphery   [%]  T1PercentPeripheralDist QTL population both 10-14wks N=122
Kumar1 29015 open field test (none) percent of distance traveled in center   [%]  T1PercentCenterDist QTL population both 10-14wks N=122
Kumar1 29016 open field test (none) percent of time in corner   [%]  T1PercentTimeCorner QTL population both 10-14wks N=122
Kumar1 29017 open field test (none) percent of time in pheriphery   [%]  T1PercentTimePheripheral QTL population both 10-14wks N=122
Kumar1 29018 open field test (none) percent of time in center   [%]  T1PercentTimeCenter QTL population both 10-14wks N=122
Kumar1 29019 open field test (none) number of crossings between periphery and center   [%]  T1TotalCrossing QTL population both 10-14wks N=122
Kumar1 29020 open field test (none) number of boli at end of open field test   [n]  FB1 QTL population both 10-14wks N=122
Kumar1 29021 body weight (none) body weight   [g]  BW1 QTL population both 10-14wks N=122
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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