MPD: Data set: Kumar1

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
Contact	Vivek Kumar vivek.kumar@jax.org
Affiliation	Churchill Group QTL Archive
Acknowledgements	We 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 identifiers	Kumar1 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 type	F2 intercross
Population size	113 ♀ 131 ♂
Age	10-14wks

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

Data set	MPD ID	Procedure / Protocol	Drug or Challenge	Phenotype Measure	Panel	Sex	Age	Sample Size (Avg)
Kumar1	29001	circadian wheel running	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	circadian wheel running	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	circadian wheel running	(none)	average speed over 30 minutes of baseline [cm x 100 / min] 1baseline_avg	QTL population	both	10-14wks	N=122

Kumar1	29004	circadian wheel running	cocaine	average speed over 30 minutes after cocaine response [cm x 100 / min] 130avg	QTL population	both	10-14wks	N=122

Kumar1	29005	circadian wheel running	cocaine	net response–baselineavg subtracted from 30avg [cm x 100 / min] 1resp-baseline	QTL population	both	10-14wks	N=122

Kumar1	29006	circadian wheel running	(none)	circadian period [h] Tau1_(ChiSq)	QTL population	both	10-14wks	N=122

Kumar1	29007	circadian wheel running	(none)	amplitude Power_FFT	QTL population	both	10-14wks	N=122

Kumar1	29008	circadian wheel running	(none)	revolutions per minute on wheels [n/min] Avg_Counts	QTL population	both	10-14wks	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)	percentage of distance traveled in corner [%] T1PercentCornerDist	QTL population	both	10-14wks	N=122

Kumar1	29014	open field test	(none)	percentage of distance traveled in periphery [%] T1PercentPeripheralDist	QTL population	both	10-14wks	N=122

Kumar1	29015	open field test	(none)	percentage of distance traveled in center [%] T1PercentCenterDist	QTL population	both	10-14wks	N=122

Kumar1	29016	open field test	(none)	percentage of time in corner [%] T1PercentTimeCorner	QTL population	both	10-14wks	N=122

Kumar1	29017	open field test	(none)	percentage of time in periphery [%] T1PercentTimePheripheral	QTL population	both	10-14wks	N=122

Kumar1	29018	open field test	(none)	percentage 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