MPD: Data set: Threadgill2

Harrill AH, Watkins PB, Su S, Ross PK, Harbourt DE, Stylianou IM, Boorman GA, Russo MW, Sackler RS, Harris SC, Smith PC, Tennant R, Bogue M, Paigen K, Harris C, Contractor T, Wiltshire T, Rusyn I, Threadgill DW. Mouse population-guided resequencing reveals that variants in CD44 contribute to acetaminophen-induced liver injury in humans. Genome Res. 2009 Sep;19(9):1507-15. Epub 2009 May 5. PubMed 19416960 FullText

Harrill AH, Ross PK, Gatti DM, Threadgill DW, Rusyn I. Population-based discovery of toxicogenomics biomarkers for hepatotoxicity using a laboratory strain diversity panel. Toxicol Sci. 2009 Jul;110(1):235-43. Epub 2009 May 6. PubMed 19420014 FullText

Threadgill2 downloads
• Download Threadgill2 project data set one row per animal, one column per trait
• Download Threadgill2 strain means, SD, N, etc. one row per strain/sex/measure

Participants	David W Threadgill Texas A&M University, College Station, TX Alison Harrill University of Arkansas for Medical Sciences, Little Rock, AR With: Ross PK, Rusyn I
Contact	David W Threadgill dwthreadgill@tamu.edu Lab web site
Part of a series:	• Phase 1 see Threadgill1 • Phase 2 (this project) Threadgill2
Acknowledgements	Funding provided by NIH ES07126, ES11391, ES10126, GM38149, RR00046, ES35513, ES25497, ES65406; US Environmental Protection Agency STAR-RD832720 For technical assistance and histology: Balletta L, Bradford B, Lodestro C, Lee D, Maki A, Kosyk O, Woods C, Clore E, Hodges N, Boorman G. For serum enzyme testing: Kim H and the Clinical Chemistry Core Facility (UNC).
Project type	Phenotype strain survey data set
MPD identifiers	Threadgill2 MPD:396
Data changelog	No updates/corrections. Initial release date: 03/2012.
Formatted citation	Click above to copy-paste the entire citation for this MPD web page.

An investigation of liver injury after oral administration of acetaminophen (N-acetyl-p-aminophenol; APAP) in various doses. The study involved 3 cohorts, including controls as well as animals treated with acetaminophen 50 and 300 mg/kg body weight. Animals were evaluated in these areas: blood and liver chemistry, serum drug and metabolite concentration, and liver pathology. Data are presented here for selected cohorts and measurements.

Summary of procedures that were conducted
• metabolic panel	Alanine transaminase (serum). Acetaminophen (several doses) vs. control.
• metabolite quantification	Glutathione.
• drug and metabolite quantification	Acetaminophen metabolite concentrations (serum) and liver protein homeostasis. Baseline vs. acetaminophen (several doses, several timepoints).
• histopathology	Liver histopathology, necrosis, injury after acetaminophen vs. control. 18h fast.

Data set	MPD ID	Procedure / Protocol	Drug or Challenge	Phenotype Measure	Panel	No. of Strains	Sex	Age	Sample Size (Avg)
Threadgill2	39602	metabolic panel	acetaminophen	alanine transaminase (serum ALT) [IU/L] 50 mg/kg 300 mg/kg	inbred	5	m	6-8wks	N=5

Threadgill2	39603	histopathology	acetaminophen	liver necrosis score [%] liver_necrosis	inbred	5	m	6-8wks	N=5

Threadgill2	39604	histopathology	acetaminophen	percent nitrotyrosine staining (marker of hepatocyte injury) [%] pct_nitrotyrosine	inbred	5	m	6-8wks	N=5

Threadgill2	39605	metabolite quantification	acetaminophen	reduced glutathione (GSH) [µmol/mg] control post-Rx 300 mg/kg	inbred	5	m	6-8wks	N=4

Threadgill2	39606	metabolite quantification	acetaminophen	percent reduced glutathione [%] control post-Rx 300 mg/kg	inbred	5	m	6-8wks	N=4

Threadgill2	39607	metabolite quantification	acetaminophen	total glutathione [µmol/mg] control post-Rx 300 mg/kg	inbred	5	m	6-8wks	N=4

Threadgill2	39609	drug and metabolite quantification	acetaminophen	serum acetaminophen (APAP), 50 mg/mL dose acetaminophen [µg/mL] baseline 0.5h 1h 2h 3h 6h	inbred	5	m	6-8wks	N=5

Threadgill2	39616	drug and metabolite quantification	acetaminophen	serum acetaminophen sulfate (APAP-sulfate), 50 mg/mL dose acetaminophen [µg/mL] baseline 0.5h 1h 2h 3h 6h	inbred	5	m	6-8wks	N=5

Threadgill2	39622	drug and metabolite quantification	acetaminophen	serum acetaminophen glucuronide (APAP-Glc), 50 mg/mL dose acetaminophen [µg/mL] baseline 0.5h 1h 2h 3h 6h	inbred	5	m	6-8wks	N=4

Threadgill2	39632	drug and metabolite quantification	acetaminophen	serum acetaminophen (APAP), 300 mg/mL dose acetaminophen [µg/mL] baseline 0.5h 1h 2h 3h 6h	inbred	5	m	6-8wks	N=5

Threadgill2	39638	drug and metabolite quantification	acetaminophen	serum acetaminophen sulfate (APAP-sulfate), 300 mg/mL dose acetaminophen [µg/mL] baseline 0.5h 1h 2h 3h 6h	inbred	5	m	6-8wks	N=5

Threadgill2	39639	drug and metabolite quantification	acetaminophen	serum acetaminophen glucuronide (APAP-Glc), 300 mg/mL dose acetaminophen [µg/mL] baseline 0.5h 1h 2h 3h 6h	inbred	5	m	6-8wks	N=5

Threadgill2: Drug study: Acetaminophen pharmakokinetics and drug-induced liver injury in males of 5 inbred strains of mice (2005)