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Updated: Feb 28, 2026
Mouse Model of Metabolic Dysfunction-Associated Steatotic Liver Disease with Fibrosis
Published on: July 18, 2025
Female GADD34 mice develop age-related inflammation and hepatocellular carcinoma
Naomi Nishio1,2, Tadao Hasegawa1, Ichiro Tatsuno1
1Department of Bacteriology, Nagoya City University, Nagoya, Japan.
Aim:
To analyze the impact of sex on GADD34 function, we studied the aging of female GADD34-deficient mice and compared them with male GADD34-deficient mice.
Methods:
We used GADD34-deficient mice on a C57BL/6 background. These mice were fed a normal diet throughout their life. Alternatively, they were fed a high-fat diet at 3 months-of-age. Liver tissues taken from mice were analyzed by hematoxylin-eosin staining and immunohistochemical methods. Fresh liver cells were analyzed by flow cytometry.
Results:
We found that female GADD34-deficient mice did not develop obesity or fatty livers. However, female GADD34-deficient mice had infiltrations of myeloid cells in the liver, followed by liver atrophy. Many female GADD34-deficient mice developed hepatocellular carcinoma, whereas female wild-type (WT) mice did not show hepatocellular carcinoma during aging. Female GADD34-deficient mice and female WT mice developed the same percentages of lymphoma. Although a high-fat diet induced a higher level of steatosis in young male GADD34-deficient mice compared with WT mice, a high-fat diet induced the same level of steatosis in young female GADD34-deficient mice compared with WT mice. However, GADD34-deficient female young mice had a higher level of infiltration of myeloid cells and myofibroblasts than WT mice.
Conclusions:
In contrast to male GADD34-deficient mice, female GADD34-deficient mice did not show obesity as they aged. However, similar to the males, they developed inflammation followed by hepatocellular carcinoma. Geriatr Gerontol Int 2017; 17: 2593-2601.
