Alms1 is an ubiquitous protein that is essential for normal primary ciliary function. Although its specific regulation mechanism has not been fully discovered, studies indicate that absent of Alms1 protein will promote nutrient absorption and increase food intake. Alms1 gene dysfunction is responsible for Alström syndrome in human. Alström syndrome is an autosomal recessive disorder of childhood obesity, type 2 diabetes, dyslipidemia, low growth hormone levels, hypothyroidism, infertility, and frequent abnormalities of kidney, heart, and liver; the latter includes steatosis and cirrhosisblindness. Mice with Alms1 gene deletion are susceptible to insulin resistance, obesity and diabetes. Futhermore, they show transition of steatosis to severe fibrosing steatohepatitis by feeding special diet.
1. Obesity, diabetes and NASH disease research.
2. Drug efficacy evaluation of metabolic disease, such as obesity, diabetes and NASH disease.
3. Drug efficacy evaluation of metabolic disease complications.
1. B6-Alms1 KO NASH body weight increased
2. B6-Alms1 KO NASH Plasma Liver Morphology (6 weeks post feeding)
3. Plasma Chol and LDL-C(6 weeks post feeding)
4.B6-Alms1 KO NASH Liver Histological（6 weeks Post WD Feeding）
The results showed that B6-ALMS1 KO mice could develop the classic symptoms of NASH within a short period of time (6 weeks), including significant systemic metabolic disorders (obesity, hyperlipidemia, etc) and severe steatosis, inflammation, hepatocytic ballooning, and fibrosis in the liver after secondary induction by Western diet. The advantages of this model are its shorter timeframe and NASH symptoms significantly. Hence, B6-ALMS1 KO mice were ideal model for preclinical NASH drug screening.