A modified choline-deficient, ethionine-supplemented diet reduces morbidity and retains a liver progenitor cell response in mice.
The choline-deficient, ethionine-supplemented (CDE) dietary model induces chronic liver damage, and stimulates liver progenitor cell (LPC)-mediated repair. Long-term CDE administration leads to hepatocellular carcinoma in rodents and lineage-tracing studies show that LPCs differentiate into functional hepatocytes in this model. The CDE diet was first modified for mice by our laboratory by separately administering choline-deficient chow and ethionine in the drinking water (CD+E diet). Although this CD+E diet is widely used, concerns with variability in weight loss, morbidity, mortality and LPC response have been raised by researchers who have adopted this model. We propose that these inconsistencies are due to differential consumption of chow and ethionine in the drinking water, and that incorporating ethionine in the choline-deficient chow, and altering the strength, will achieve better outcomes. Therefore, C57Bl/6 mice, 5 and 6 weeks of age, were fed an all-inclusive CDE diet of various strengths (67% to 100%) for 3 weeks. The LPC response was quantitated and cell lines were derived. We found that animal survival, LPC response and liver damage are correlated with CDE diet strength. The 67% and 75% CDE diet administered to mice older than 5 weeks and greater than 18 g provides a consistent and acceptable level of animal welfare and induces a substantial LPC response, permitting their isolation and establishment of cell lines. This study shows that an all-inclusive CDE diet for mice reproducibly induces an LPC response conducive to in vivo studies and isolation, whilst minimizing morbidity and mortality.
School of Chemistry and Biochemistry, The University of Western Australia, Crawley, Western Australia 6009, Australia Cancer and Cell Biology Division, The Harry Perkins Institute of Medical Research, Nedlands, Western Australia 6009, Australia.
Adam M
AM
Passman
School of Chemistry and Biochemistry, The University of Western Australia, Crawley, Western Australia 6009, Australia Cancer and Cell Biology Division, The Harry Perkins Institute of Medical Research, Nedlands, Western Australia 6009, Australia.
Robyn P
RP
Strauss
School of Chemistry and Biochemistry, The University of Western Australia, Crawley, Western Australia 6009, Australia Cancer and Cell Biology Division, The Harry Perkins Institute of Medical Research, Nedlands, Western Australia 6009, Australia.
Sarah B
SB
McSpadden
School of Chemistry and Biochemistry, The University of Western Australia, Crawley, Western Australia 6009, Australia Cancer and Cell Biology Division, The Harry Perkins Institute of Medical Research, Nedlands, Western Australia 6009, Australia.
Megan L
ML
Finch-Edmondson
School of Chemistry and Biochemistry, The University of Western Australia, Crawley, Western Australia 6009, Australia Cancer and Cell Biology Division, The Harry Perkins Institute of Medical Research, Nedlands, Western Australia 6009, Australia.
Ken H
KH
Woo
Cancer and Cell Biology Division, The Harry Perkins Institute of Medical Research, Nedlands, Western Australia 6009, Australia.
Luke A
LA
Diepeveen
School of Chemistry and Biochemistry, The University of Western Australia, Crawley, Western Australia 6009, Australia Cancer and Cell Biology Division, The Harry Perkins Institute of Medical Research, Nedlands, Western Australia 6009, Australia.
Roslyn
R
London
School of Chemistry and Biochemistry, The University of Western Australia, Crawley, Western Australia 6009, Australia School of Health Sciences, The University of Notre Dame Australia, Fremantle, Western Australia 6959, Australia.
Bernard A
BA
Callus
School of Chemistry and Biochemistry, The University of Western Australia, Crawley, Western Australia 6009, Australia Cancer and Cell Biology Division, The Harry Perkins Institute of Medical Research, Nedlands, Western Australia 6009, Australia George.Yeoh@uwa.edu.au.
George C
GC
Yeoh
D000375:Aging; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001652:Bile Ducts / Q000166:cytology; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D002794:Choline / Q000494:pharmacology*; D004032:Diet; D005001:Ethionine / Q000494:pharmacology*; D022781:Hepatocytes / Q000166:cytology; D007249:Inflammation / Q000473:pathology; D008099:Liver / Q000166:cytology* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D009017:Morbidity; D013234:Stem Cells / Q000166:cytology*; D016019:Survival Analysis
D015415:Biomarkers; D000410:Alanine Transaminase; D002794:Choline; D005001:Ethionine
Ductular reaction; Fatty liver; Hepatic stem cell; Hepatocarcinogenesis; Regeneration