MPD: Data set: Threadgill1

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

Threadgill1 downloads
• Download Threadgill1 project data set animal data, as uploaded
• Download Threadgill1 animal data matrix with factor-related expansion applied as necessary
• Download Threadgill1 strain means, SD, N, etc. one row per strain/sex/measure
• Threadgill1 supplementary data

Ontology terms mapped to Threadgill1 measures:

MA:0000358 liver
MA:0002502 serum
MP:0000203 abnormal circulating aspartate transaminase level
MP:0001573 abnormal circulating alanine transaminase level
MP:0001654 hepatic necrosis
MP:0004847 abnormal liver weight
MP:0005265 abnormal blood urea nitrogen level
MP:0008469 abnormal protein level
MP:0008872 abnormal physiological response to xenobiotic
MP:0011592 abnormal catalase activity
MP:0011601 abnormal glutathione peroxidase activity
VT:0000203 blood aspartate transaminase amount
VT:0000598 liver morphology trait
VT:0000609 liver physiology trait
VT:0001573 blood alanine transaminase amount
VT:0003402 liver mass
VT:0005265 blood urea nitrogen amount
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 Ivan Rusyn Texas A&M University, College Station, TX
Participants	Ross PK
Contact	David W Threadgill dwthreadgill@tamu.edu Lab web site
Part of a series:	• Phase 1 (this project) Threadgill1 • Phase 2 see 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	Threadgill1 MPD:194
Data changelog	1 update/correction. Initial release date: 02/2009.
Formatted citation	Click above to copy-paste the entire citation for this MPD web page.

An investigation of liver injury after administration of acetaminophen (N-acetyl-p-aminophenol; APAP) in various doses. The study involved 8 cohorts, including controls as well as animals treated with acetaminophen 30, 100, 200, 300, 600, 900, and 1200 mg/kg body weight. Animals were evaluated in these areas: blood and liver chemistry, liver function, and alterations in liver morphology. Data are presented here for selected cohorts and measurements.

Procedures conducted:

• metabolic panel		Blood urea nitrogen, alanine transaminase, aspartate transaminase (serum), liver enzyme homeostasis. Acetaminophen (several doses) vs. control, several timepoints post-Rx. 18h fast.
• histopathology		Liver histopathology, necrosis after acetaminophen vs. control. 18h fast.
• metabolite quantification		Liver protein homeostasis. Acetaminophen vs. control. 18h fast.
• biomarker quantification		Liver cytochrome isoforms. Acetaminophen vs. control. 18h fast.
• organ weights		Liver weight after acetaminophen (several doses) 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)
Threadgill1:1	Threadgill1	organ weights	acetaminophen	liver weight 24h after treatment [g] liverwt 19401 dose (mg/kg): control 100 200 300	inbred w/CC7	37	m	8-17wks	N=4

Threadgill1:4	Threadgill1	histopathology	acetaminophen	necrosis [%] liver_necrosis 19404 dose (mg/kg): control 100 200 300	inbred w/CC7	37	m	8-17wks	N=2

Threadgill1:6	Threadgill1	metabolic panel	acetaminophen	alanine transaminase (serum ALT) [IU/L] ALT_ctrl 19406	inbred w/CC7	37	m	8-17wks	N=2

Threadgill1:7	Threadgill1	metabolic panel	acetaminophen	alanine transaminase (serum ALT), t=4h [IU/L] ALT_Rx100_4h 19407	inbred w/CC7	7	m	8-17wks	N=4

Threadgill1:8	Threadgill1	metabolic panel	acetaminophen	alanine transaminase (serum ALT), t=12h [IU/L] ALT_Rx100_12h 19408	inbred w/CC7	7	m	8-17wks	N=4

Threadgill1:9	Threadgill1	metabolic panel	acetaminophen	alanine transaminase (serum ALT), t=24h [IU/L] ALT_Rx100_24h 19409	inbred w/CC7	7	m	8-17wks	N=3

Threadgill1:10	Threadgill1	metabolic panel	acetaminophen	aspartate transaminase (serum AST) [IU/L] AST 19410 dose (mg/kg): control 100 200 300	inbred w/CC7	37	m	8-17wks	N=2

Threadgill1:12	Threadgill1	metabolic panel	acetaminophen	blood urea nitrogen (serum BUN) [mg/dL] BUN 19412 dose (mg/kg) control 100 200 300	inbred w/CC7	37	m	8-17wks	N=2

Threadgill1:14	Threadgill1	metabolite quantification	acetaminophen	reduced glutathione (GSH) [µmol/g] GSH 19414 control post-Rx 300mg/kg	inbred w/CC7	36	m	8-17wks	N=2

Threadgill1:16	Threadgill1	metabolite quantification	acetaminophen	oxidized glutathione (GSSG) [µmol/g] GSSG 19416 control post-Rx 300mg/kg	inbred w/CC7	36	m	8-17wks	N=2

Threadgill1:18	Threadgill1	metabolite quantification	acetaminophen	total glutathione (GSH plus GSSG) [µmol/g] GSH_total 19418 control post-Rx 300 mg/kg	inbred w/CC7	36	m	8-17wks	N=2

Threadgill1:20	Threadgill1	metabolite quantification	acetaminophen	ratio of reduced (GSH) to oxidized (GSSG) glutathione [ratio] GSHratio 19420 control post-Rx 300mg/kg	inbred w/CC7	36	m	8-17wks	N=2

Threadgill1:82	Threadgill1	metabolic panel	acetaminophen	catalase [µg/mL] catalase 19482 control post-Rx 300 mg/kg	inbred w/CC7	37	m	8-12wks	N=2

Threadgill1:83	Threadgill1	biomarker quantification	acetaminophen	cytochrome P450 1A2 isoform [pmol/mg] CYP1A2 19483 control post-Rx 300 mg/kg	inbred w/CC7	37	m	8-12wks	N=2

Threadgill1:84	Threadgill1	biomarker quantification	acetaminophen	cytochrome P450 2E1 isoform [pmol/mg] CYP2E1 19484 control post-Rx 300 mg/kg	inbred w/CC7	37	m	8-12wks	N=2

Threadgill1:86	Threadgill1	metabolite quantification	acetaminophen	glutathione transferase [µg/mL] GSTpi 19486 control post-Rx 300 mg/kg	inbred w/CC7	37	m	8-12wks	N=2

Threadgill1:98	Threadgill1	colony observation	(none)	age at testing (local parameter) [wks] age 19498	inbred w/CC7	37	m		N=17

Threadgill1: Drug study: Toxicogenetic survey of susceptibility to acetaminophen-induced liver injury in males of 37 inbred strains of mice (2005)

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