Pruniau et al. observed growth defects and metabolic abnormalities in mice expressing the Cre recombinase in the liver under control of the albumin promoter and albumin/α-fetoprotein enhancer (AlfpCre). We agree that these findings imply careful interpretation of data, but their letter does not reflect correct interpretation of our findings.
The authors claim, based on their data, that GH-deficiency in AlfpCre mice causes steatosis and up-regulation of genes involved in lipid uptake and synthesis.
First, Stat5AlfpCre as well as Stat5AlfpCre;GRAlfpCre mice display hepatic GH resistance, which is characterized by a 3- to 8-fold increase of murine (m) GH in plasma compared to age- and sex-matched AlfpCre negative littermates. GRAlfpCre mice show plasma mGH concentrations comparable to control mice. Moreover, the presence of the Cre transgene in GRAlfpCre mice does not lead to hepatic steatosis and up-regulation of genes involved in hepatic lipid synthesis and uptake. Second, our data resemble findings published by the Hennighausen laboratory, which report that Stat5 deletion causes hepatic steatosis and carcinoma formation using Alb-Cre mice.[2, 3]
Additionally, we examined body weights of 2-month-old Stat5loxP/loxP;GRloxP/loxP;Tg:AlfpCre/0, Stat5flox/+;GRloxP/+, and Stat5loxP/+;GRloxP/+; Tg:AlfpCre/0 male littermates. There were no significant differences in body weights of mice lacking the AlfpCre transgene and Stat5loxP/+;GRloxP/+;Tg:AlfpCre/0 mice (Fig. 1). In contrast, Stat5loxP/loxP;GRloxP/loxP;Tg:AlfpCre/0 animals show a severely reduced body weight (Fig. 1). For comparison purposes, we provide the body weights of 2-month-old Stat5ΔN mice (no Cre), which have a growth defect due to impaired STAT5-GR protein-protein interaction.
In brief, the origin, backcrossing procedure, and transmission route for AlfpCre transgenic mice, dietary, and mouse house conditions used by Pruniau et al. are missing. Their C57BL/6 growth curves are puzzling and indicative of dwarfism in wild-type controls. Experimental group sizes were small and prolonged growth curves for both sexes are essential and should not be presented in a linear manner.
Kristina M. Mueller, Dipl. Ing.Richard Moriggl, Ph.D.
Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria