Liver Tumor Model in Pten-Deficient Mice

All animal work was conducted in accordance with national guidelines and was approved by the Institutional Animal Care and Use Committee (IACUC) at the University of Washington, Seattle. 8 week old male albumin (Alb)-Cre mice (003574, B6.Cg-Tg(Alb-cre)21Mgn/J) and 8-week old female Pten^fl/fl mice (006440, B6.129S4-Ptentm1Hwu/J) were purchased from Jackson Laboratory (Bar Harbor, ME). Alb-Cre mice were bred with Pten^fl/fl mice to ultimately generate Pten^fl/fl;Alb^cre experimental mice. Genotyping protocols and primers were obtained from Jackson Laboratory, and PCR was performed to confirm the correct genotype. At 40 weeks of age, Pten^fl/fl;Alb^cre (Pten-null) mice develop tumors that are physiologically similar to human HCCs and ICCs (intrahepatic cholangiocarcinoma) (Horie et al., 2004 (link); Kenerson et al., 2011 (link)). Moreover, the mice develop hepatic steatosis, resulting in livers that are abnormally large preceding tumorigenesis. Tumor progression was monitored through weekly ultrasound scans with an L15-7io imaging probe on a Philips iU22 (Philips Medical Systems, Bothell, WA) starting at 36 weeks of age. Mice (20 male and 18 female) were treated once tumors were 1 cm in diameter.

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Keller S.B., Suo D., Wang Y.N., Kenerson H., Yeung R.S, & Averkiou M.A. (2020). Image-Guided Treatment of Primary Liver Cancer in Mice Leads to Vascular Disruption and Increased Drug Penetration. Frontiers in Pharmacology, 11, 584344.

Publication 2020

B6.Cg-Tg(Alb-cre)21Mgn/J Ptenfl/fl mice B6.129S4-Ptentm1Hwu/J)

Albumin Animal Female Genotype Hccs Hepatic steatosis Human Iccs Institutional animal care and use committee Intrahepatic cholangiocarcinoma Livers Male Mice Null mice Primers Progression Pten Scans ultrasound Tumorigenesis Tumors

Corresponding Organization : University of Washington

Other organizations : University of Washington Applied Physics Laboratory

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Variable analysis

independent variables

Genotype: Pten^fl/fl;Alb^cre (Pten-null) mice

dependent variables

Tumor progression
Hepatic steatosis (abnormally large livers)

control variables

Age of mice: 8 weeks old at the start of the experiment
Sex of mice: Male Alb-Cre mice and female Pten^fl/fl mice
Genotyping protocols and primers from Jackson Laboratory
Weekly ultrasound scans to monitor tumor progression

controls

Positive control: Wild-type or Pten^fl/fl mice (not explicitly mentioned)
Negative control: Not explicitly mentioned

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