The Establishment Of A Mouse Model Of Human Hyperammonemia

Congenital hyperammonemia is caused by urea synthesis of congenital metabolic abnormalities,resulting in increased blood ammonia,causing damage to the nervous system diseases.Because the enzyme in urea circulation has hereditary defect,and that urea synthesis obstacle.Hyperammonemia is a common clinical disease while the brain injury is the main reason of dementia and mental decline,and even life-threatening in severe cases.So far,China has not been reported in animal models of stable inheritance of hyperammonemia.In this study,an abnormal growth of 129 mice(mutant mice)was found in the experiment.And showed high amino acid hyperlipidemia and human clinical manifestations of hyperammonemia,as well as biochemical indicators are very similar,and human genetic metabolic diseases with great relevance.The establishment of the animal model of the disease will fill the gap in the animal model of ammonia in China.To establish high blood ammonia mouse model and develop new drugs for hyperammonemia,efficacy evaluation,therapeutic research and gene therapy research which will play a good role in social benefits.This project analyzed the similarity between hyperammonemia and human hyperammonemia by using the correct genetic breeding methods and further studying the biological characteristics,pathology,metabolic disorders and enzyme relationship of hyperammonemia mice.The similarity of hyperammonemia in mice and human hyperammonemia was analyzed.In the genealogical analysis of mutant mice,it was found that the proportion of the generation of mutant mice showed a trend of 1/4 proportion and the occurrence of heterozygotes was not related to gender,so it was an autosomal recessive inheritance.Analysis of its biological characteristics showed that the average life span of the mutant mice was only 18 days,the longest 25 days and the shortest 6 days;Biochemical characteristics,Blood biochemical and blood tests showed that total cholesterol and triglycerides are high in this mutant mice;low blood sugar level;rarely blood platelets;Tandem mass spectrometry analysis of plasma acyl carnitine found that short,medium and long chain acyl carnitine have significant or extremely significant increase in the acyl carnitine accumulation,concentration of C4,C6,C8,C10,C14 and C16 has increased);Pathological analysis showed that the major organs of mutant mice were significantly higher than those in the control group.Studies have shown that the hyperammonemia mice are single gene recessive inheritance,which can truly reflect the clinical manifestations of human hyperammonemia,biochemical indicators,metabolic changes and other symptoms and signs.So the mutant mice could be used to establish a model of hyperammonemia in the future.