Construction method and application of glycogen accumulation disease Ib type gene point mutation mouse model

Abstract

The invention relates to the technical field of animal model construction, in particular to a construction method and application of a glycogen accumulation disease Ib type gene point mutation mouse model. A homozygous mouse model with SLC37A4 gene point mutation is obtained by a method of hybridizing a heterozygous mouse with the SLC37A4 gene point mutation with other strains of wild type mice, and is used for truly simulating clinical diseases of patients with glycogen accumulation disease Ib caused by SLC37A4 gene defects due to the SLC37A4 gene point mutation. The point mutation mouse model obtained by adopting the construction method can be applied to research on pathogenesis of the glycogen accumulation disease Ib and development of drugs for treating the glycogen accumulation disease Ib.

Description

technical field [0001] The invention relates to the technical field of animal model construction, in particular to a construction method and application of a glycogen accumulation disease type Ib gene point mutation mouse model. Background technique [0002] Type I glycogen storage disease (glycogen storage disease type I, GSD Ⅰ) is caused by gene mutations that lead to decreased enzyme efficiency of glucose-6-phosphatase (G6Pase), abnormal glycogenolysis and gluconeogenesis metabolism. Inherited metabolic defect disease is the most common type of hepatic glycogen accumulation disease, and it is a single-gene genetic disease listed in the "First List of Rare Diseases". The main clinical manifestations are growth retardation, hypoglycemia, hepatomegaly, hyperlactic acidemia, hyperuricemia, hypertriglyceridemia, metabolic acidosis, etc. Children often die of severe hypoglycemia and metabolic acidosis . [0003] GSD Ⅰ is divided into two types, Ia and Ib, according to the pat...

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Problems solved by technology

For example, the whole-body SLC37A4 gene conditional knockout mice reported for the first time in 2003 can basically simulate clinical characteristics, but a special feeding program of feeding glucose every 12 hours is required to make the mice survive until weaning; reports in 2018 respectively constructed Small intestine, liver, and bone marrow conditional knockout of SLC37A4 gene mice, the mice survived well and could survive for up to 6 months, but the clinical symptoms were mild, and it was difficult to simulate clinical patients

Both of the above two SLC37A4 gene-deficient mouse models were constructed by gene editing technology to knock out the SLC37A4 gene systemically or in tissues. In fact, the way of causing the SLC37A4 gene defect in GSD Ⅰb patients has obvious regional characteristics and is not Not all GSD Ⅰb patients with SLC37A4 gene defect can be simulated by knockout. For example, the SLC37A4 gene defect in China is caused by a point mutation of the gene. Therefore, the SLC37A4 gene mutant mouse model obtained by gene knockout cannot be simulated. for precision medicine research

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