MPD: Data set: Harrill2

Harrill AH, Desmet KD, Wolf KK, Bridges AS, Eaddy JS, Kurtz CL, Hall JE, Paine MF, Tidwell RR, Watkins PB. A Mouse Diversity Panel Approach Reveals the Potential for Clinical Kidney Injury Due to DB289 Not Predicted by Classical Rodent Models. Toxicol Sci. 2012 Dec;130(2):416-26. doi: 10.1093/toxsci/kfs238. Epub 2012 Aug 31. PubMed 22940726 FullText

Notes
"Difference" measurements were computed by MPD from the strain means (fold change, D289 over control) and are available for download in a separate supplementary file.

MPD curation note: DB289 was previously tested in clinical trials to treat African trypanosomiasis. However, the trial was terminated when subjects developed severe kidney injury, an effect not predicted from preclinical testing. This project (Harrill2) highlights the utility of inbred strains to predict clinically relevant toxicities to drugs prior to clinical trials.

Harrill2 downloads
• Download Harrill2 project data set animal data, as uploaded
• Download Harrill2 animal data matrix with factor-related expansion applied as necessary
• Download Harrill2 strain means, SD, N, etc. one row per strain/sex/measure
• Harrill2 supplementary data

Ontology terms mapped to Harrill2 measures:

MA:0000325 urinary system
MA:0000358 liver
MA:0000368 kidney
MA:0002502 serum
MA:0002545 urine
MP:0001259 abnormal body weight
MP:0001573 abnormal circulating alanine transaminase level
MP:0002707 abnormal kidney weight
MP:0004847 abnormal liver weight
MP:0005265 abnormal blood urea nitrogen level
MP:0005328 abnormal circulating creatinine level
MP:0006315 abnormal urine protein level
MP:0008872 abnormal physiological response to xenobiotic
MP:0008875 abnormal xenobiotic pharmacokinetics
MP:0011469 abnormal urine creatinine level
MP:0011923 abnormal bladder urine volume
VT:0001259 body mass
VT:0001573 blood alanine transaminase amount
VT:0001756 urine production trait
VT:0001757 urine molecular composition trait
VT:0002136 kidney physiology trait
VT:0002707 kidney mass
VT:0003402 liver mass
VT:0005265 blood urea nitrogen amount
VT:0005328 blood creatinine amount
VT:0010487 response to xenobiotic stimulus trait

Investigators	Alison Harrill University of Arkansas for Medical Sciences, Little Rock, AR
Contact	Alison Harrill AHHarrill@uams.edu Lab web site
Acknowledgements	Funding provided by the Bill and Melinda Gates Foundation.
Project type	Phenotype strain survey data set
MPD identifiers	Harrill2 MPD:441
Data changelog	No updates/corrections. Initial release date: 12/2012.
Formatted citation	Click above to copy-paste the entire citation for this MPD web page.

Mice received ten days of oral treatment with DB289 (pafuramidine) or vehicle. Blood chemistry and urinalysis were performed. Urine biomarkers of kidney injury were measured and organs weighed.

Procedures conducted:

• body weight		DB289-treated vs. control.
• metabolic panel		Blood urea nitrogen, alanine transaminase, creatinine. DB289-treated vs. control.
• urinalysis		Urine volume, creatinine. DB289-treated vs. control.
• biomarker quantification		Kidney injury molecule 1 (KIM-1). DB289-treated vs. control.
• organ weights		Kidney and liver weights. DB289-treated vs. control.
• drug and metabolite quantification		Kidney metabolite (DB75) concentration. DB289-treated vs. control.

Harrill2: Drug study: Survey of kidney injury due to DB289 treatment in females of 34 inbred strains of mice (2012)

Filter Table Results

Sort/ Pick	Data set	Procedure / Protocol	Treatment	Phenotype Measure / Variable (click to view)	Panel	No. of Strains	Sex	Age	Sample Size (Avg)
Harrill2:1	Harrill2	body weight	DB289	body weight at start of testing [g] bw_start 44101 control DB289	inbred	34	f	6-8wks	N=5

Harrill2:3	Harrill2	body weight	DB289	body weight at end of testing [g] bw_end 44103 control DB289	inbred	34	f	6-8wks	N=5

Harrill2:5	Harrill2	body weight	DB289	fold change in body weight over testing period [ratio] bw_change 44105 control DB289 difference	inbred	34	f	6-8wks	N=5

Harrill2:11	Harrill2	metabolic panel	DB289	alanine transaminase (serum ALT) [IU/L] ALT 44111 control DB289 difference	inbred	34	f	6-8wks	N=5

Harrill2:15	Harrill2	metabolic panel	DB289	blood urea nitrogen (serum BUN) [mg/dL] BUN 44115 control DB289 difference	inbred	34	f	6-8wks	N=5

Harrill2:21	Harrill2	metabolic panel	DB289	creatinine (serum CREA) [mg/dL] serum_CREA 44121 control DB289 difference	inbred	34	f	6-8wks	N=5

Harrill2:25	Harrill2	urinalysis	DB289	urine volume [mL] urine_vol 44125 control DB289 difference	inbred	33	f	6-8wks	N=5

Harrill2:31	Harrill2	urinalysis	DB289	creatinine (urine CREA) [mg/mL] urine_CREA 44131 control DB289 difference	inbred	31	f	6-8wks	N=5

Harrill2:35	Harrill2	biomarker quantification	DB289	urine kidney injury molecule 1 (KIM-1) [pg] urine_KIM1 44135 control DB289 difference	inbred	33	f	6-8wks	N=4

Harrill2:41	Harrill2	organ weights	DB289	kidney (left) weight [g] Lt_kidney 44141 control DB289	inbred	34	f	6-8wks	N=5

Harrill2:44	Harrill2	organ weights	DB289	kidney (right) weight [g] Rt_kidney 44144 control DB289	inbred	34	f	6-8wks	N=5

Harrill2:48	Harrill2	organ weights	DB289	kidney (both) weight [g] both_kidney 44148 control DB289	inbred	34	f	6-8wks	N=5

Harrill2:51	Harrill2	organ weights	DB289	total kidney weight as percentage of body weight [%] pctKW_BW 44151 control DB289 difference	inbred	34	f	6-8wks	N=5

Harrill2:55	Harrill2	drug and metabolite quantification	DB289	kidney metabolite (DB75) concentration [µM] kidney_DB75 44155 control DB289	inbred	34	f	6-8wks	N=4

Harrill2:61	Harrill2	organ weights	DB289	liver weight at sacrifice [g] LW 44161 control DB289	inbred	34	f	6-8wks	N=5

Harrill2:65	Harrill2	organ weights	DB289	liver weight as percentage of body weight [%] pctLW_BW 44165 control DB289 difference	inbred	34	f	6-8wks	N=5