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 animal data, as uploaded
• Download Threadgill2 animal data matrix with factor-related expansion applied as necessary
• Download Threadgill2 strain means, SD, N, etc. one row per strain/sex/measure

Ontology terms mapped to Threadgill2 measures:
MA:0000358 liver
MA:0002502 serum
MP:0000598 abnormal liver morphology
MP:0000607 abnormal hepatocyte morphology
MP:0001573 abnormal circulating alanine transaminase level
MP:0001654 hepatic necrosis
MP:0008872 abnormal physiological response to xenobiotic
MP:0011601 abnormal glutathione peroxidase activity
MP:0012691 abnormal acetaminophen metabolism
VT:0000598 liver morphology trait
VT:0000609 liver physiology trait
VT:0001573 blood alanine transaminase amount
VT:0002121 metabolism trait
VT:0010487 response to xenobiotic stimulus trait
VT:0010516 blood glutathione amount

Investigators	David W Threadgill Texas A&M University, College Station, TX Alison Harrill University of Arkansas for Medical Sciences, Little Rock, AR
Participants	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.

Procedures 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.

Sort/ Pick	Data set	Procedure / Protocol	Treatment	Phenotype Measure / Variable (click to view)	Panel	No. of Strains	Sex	Age	Sample Size (Avg)
Threadgill2:2	Threadgill2	metabolic panel	acetaminophen	alanine transaminase (serum ALT) [IU/L] ALT 39602 50 mg/kg 300 mg/kg	inbred	5	m	6-8wks	N=5

Threadgill2:3	Threadgill2	histopathology	acetaminophen	liver necrosis score [%] liver_necrosis 39603	inbred	5	m	6-8wks	N=5

Threadgill2:4	Threadgill2	histopathology	acetaminophen	percent nitrotyrosine staining (marker of hepatocyte injury) [%] pct_nitrotyrosine 39604	inbred	5	m	6-8wks	N=5

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

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

Threadgill2:7	Threadgill2	metabolite quantification	acetaminophen	total glutathione [µmol/mg] GSH_total 39607 control post-Rx 300 mg/kg	inbred	5	m	6-8wks	N=4

Threadgill2:9	Threadgill2	drug and metabolite quantification	acetaminophen	serum acetaminophen (APAP), 50 mg/mL dose acetaminophen [µg/mL] APAP50 39609 baseline 0.5h 1h 2h 3h 6h	inbred	5	m	6-8wks	N=5

Threadgill2:16	Threadgill2	drug and metabolite quantification	acetaminophen	serum acetaminophen sulfate (APAP-sulfate), 50 mg/mL dose acetaminophen [µg/mL] APAP_Sulf_50 39616 baseline 0.5h 1h 2h 3h 6h	inbred	5	m	6-8wks	N=5

Threadgill2:22	Threadgill2	drug and metabolite quantification	acetaminophen	serum acetaminophen glucuronide (APAP-Glc), 50 mg/mL dose acetaminophen [µg/mL] APAP_Glc_50 39622 baseline 0.5h 1h 2h 3h 6h	inbred	5	m	6-8wks	N=4

Threadgill2:32	Threadgill2	drug and metabolite quantification	acetaminophen	serum acetaminophen (APAP), 300 mg/mL dose acetaminophen [µg/mL] APAP300 39632 baseline 0.5h 1h 2h 3h 6h	inbred	5	m	6-8wks	N=5

Threadgill2:38	Threadgill2	drug and metabolite quantification	acetaminophen	serum acetaminophen sulfate (APAP-sulfate), 300 mg/mL dose acetaminophen [µg/mL] APAP_Sulf_300 39638 baseline 0.5h 1h 2h 3h 6h	inbred	5	m	6-8wks	N=5

Threadgill2:39	Threadgill2	drug and metabolite quantification	acetaminophen	serum acetaminophen glucuronide (APAP-Glc), 300 mg/mL dose acetaminophen [µg/mL] APAP_Glc_300 39639 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)