Using CRISPR/cas9 technology， sgRNA/cas9 mRNA effectively identifying exons 2 and 18 of LDLR gene was injected into the fertilized eggs of NOD SCID mice. The gene knockout F0 positive （LDLR^+/+， AA） mice were screened by genotyping of neonatal mice， and the mice were bred with NOD SCID （LDLR^+/+， AA） mice to identify the F1 generation （AA） with stable genotypes mice. The F1 positive heterozygous mice and NOD SCID mice were bred to obtain a large number of F2 generation （AA） mice with exactly the same gene sequence. Large scale breeding was carried out between F2 generations.The F3 generation mice were grouped according to genotype and gender， respectively： male AA， male Aa， female AA and female Aa.The body weights were monitored， and the peripheral blood was collected for blood cholesterol level detection.

The NOD SCID LDLR^+/－ （AA） mice were obtained by the above construction method. After 8 weeks of weight detection， it was found that Aa heterozygous genotype did not affect the body weight of mice during growth and development process. The cholesterol level of female Aa was （100.80±4.42） mg·dL^－1 and male Aa was （120.56±11.16） mg·dL^－1， compared with negative control （AA mice），the cholesterol levels were significantly increased（P<0.05）；the cholesterol levels of female AA and male AA were（60.78±2.11） and （75.43±10.06） mg·dL^－1，and the difference between them was statistically significant （P<0.05）.

Without affecting the body weight of mice， a mouse model with spontaneous increase of cholesterol level is successfully constructed by using CRISPR/cas9 technology under the background of NOD SCID， which can be used as the basis for humanization.