Consistently, both circulating levels of FGF21 and its hepatic mRNA expression were progressively elevated in apoE−/− mice with spontaneous development of hypercholesterolemia and atherosclerosis.
In fact, chronic hepatic SAM deficiency in a certain mouse strain (i.e., Mat1a knockout mice) resulted in spontaneous development of HCC (Martinez-Chantar et al. 2002).
Thus, we can add the Splunc1 −/− mouse to the list of models that feature spontaneous chronic otitis media as a component of their phenotype.
In contrast, PTP1B effectively inhibits signaling of several oncogenic tyrosine kinases [ 50], while inactivation of the gene in TP53 knockout mice accelerates the spontaneous development of lymphomas [ 32].
The monoallelic deletion of BECLIN 1 in mice caused the spontaneous development of tumours, including ovarian cancer, in association with reduced autophagy [ 11].
MET overexpression in transgenic mice led to spontaneous development of hepatocellular carcinoma and and inactivation of the MET gene to tumor regression [ 41].
Non-obese diabetic (NOD) mice = a mouse strain susceptible to spontaneous development of autoimmune insulin dependent diabetes mellitus.
Changing environmental factors in the housing conditions of DBA/1 mice severely affects the spontaneous development of arthritis.
Twenty-eight p53+/- Atm+/-, 22 p53+/- Atm+/+, 11 p53+/+ Atm+/- and 25 p53+/+ Atm+/+ mice were examined for spontaneous development of tumours until age 26 months (113 weeks).
Two interesting reports have shown spontaneous development of synovitis and cartilage degeneration in transgenic mice, which overexpress cathepsin K (transgenic UTU17 mice) [ 10, 11].
The insertion of a 2-kb DNA fragment termed "clone B" in these transgenic mice, however, lead to the spontaneous development of cutaneous melanoma [ 22].
