Name: Ldlr KO (em) Mouse
Brand: サイヤジェン（Cyagen）
SKU: C001392

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Ldlr KO (em) Mouse

製品名

Ldlr KO (em) Mouse

製品ID

C001392

系統名

C57BL/6JCya-Ldlr^em2/Cya

背景情報

C57BL/6JCya

状況

このマウス系統を論文で使用する場合は、「Ldlr KO (em) Mouse（カタログ番号C001392）はサイアジェンから購入しました。」と引用してください。

Disease Animal Models

Obesity and Diabetes Mellitus

Atherosclerosis

製品タイプ

年齢

遺伝子型

性別

数量

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Disease Animal Models

Obesity and Diabetes Mellitus

Atherosclerosis

基本情報

検証 Data

系統詳細

The Low-density lipoprotein receptor (LDLR) gene encodes a protein that is one of the hepatocyte surface receptors that binds apolipoprotein E (APOE) and thus removes lipoprotein particles from the blood. LDLR also plays an important role in cholesterol homeostasis by interacting with apolipoprotein B (APOB) on low-density lipoprotein (LDL) particles (the major cholesterol-carrying lipoprotein in plasma) to bind LDL and transport it into cells by endocytosis, thus maintaining plasma LDL levels ^[1-2]. This process occurs mainly in the liver, which removes approximately 70% of LDL from the circulation, and LDLR regulates plasma cholesterol levels by removing LDL and intermediate-density lipoproteins (IDL) from the plasma. Loss-of-function mutations in the LDLR gene cause familial hypercholesterolemia (FHCL1), a lipoprotein disorder characterized by elevated LDL cholesterol levels. The disease causes excessive deposition of cholesterol in tissues, which subsequently leads to macular tumors, accelerated atherosclerosis, and an increased risk of premature coronary heart disease ^[3-4].

This strain is an Ldlr deletion mouse model that uses gene editing technology to knock out the expression of human LDLR gene homolog in mice with impaired LDLR receptor synthesis, resulting in elevated serum cholesterol levels, which are further exacerbated by feeding on a high-fat diet (HFD), and the formation of aortic plaques. Homozygous Ldlr KO mice are viable and fertile and can be used for studies such as hypercholesterolemia and atherosclerosis. A similar strain includes Ldlr KO (tm) (catalog number: C001278), which was constructed using embryonic stem (ES) cell technology.

参考文献

Brown MS, Goldstein JL. A receptor-mediated pathway for cholesterol homeostasis. Science. 1986 Apr 4;232(4746):34-47.

Go GW, Mani A. Low-density lipoprotein receptor (LDLR) family orchestrates cholesterol homeostasis. Yale J Biol Med. 2012 Mar;85(1):19-28.

Ishibashi S, Brown MS, Goldstein JL, Gerard RD, Hammer RE, Herz J. Hypercholesterolemia in low density lipoprotein receptor knockout mice and its reversal by adenovirus-mediated gene delivery. J Clin Invest. 1993 Aug;92(2):883-93.

Witztum JL. Murine models for study of lipoprotein metabolism and atherosclerosis. J Clin Invest. 1993 Aug;92(2):536-7.

系統作製戦略

The Ldlr gene is located on mouse chromosome 9, and exon 4 of the gene was selected as the target region for gene editing.

Figure 1. Diagram of the gene editing strategy for the generation of Ldlr KO (em) mice.

適用分野

The Ldlr KO mice can be used in research on atherosclerosis, macular tumor and coronary artery disease, familial hypercholesterolemia (FHCL1), and other metabolic and cardiovascular diseases, and screening of vasodilator drugs.

検証 Data

1. Protein expression

Figure 2. Detection of LDLR protein in the liver of Ldlr KO(em) and wild-type (WT) mice. Western Blot results show that there is no expression of LDLR protein in the liver of Ldlr KO(em) mice.

2. The growth curve

Figure 3. Detection of body weight in male wild-type and Ldlr KO (em) mice. Mice were grouped and given different diets, and their body weights in male wild-type mice (WT-M) and male Ldlr KO mice (LDLR^-/--M) were measured weekly under common and high-fat diets. The results showed similar trends in body weight between male Ldlr KO mice and male wild-type mice under a common diet (CD) and high-fat diet (HFD) similar trends with no significant differences.

3. The growth curve

Figure 4. Detection of body weight in female wild-type and Ldlr KO (em) mice. Mice were grouped and given different diets, and their body weights in female wild-type mice (WT-F) and female Ldlr KO mice (LDLR^-/--F) were measured weekly under a common diet and high-fat diet. The results showed similar trends in body weight between female Ldlr KO mice and female wild-type mice under a common diet (CD) and high-fat diet (HFD) with no significant differences.

4. Biochemical indexes of blood lipids in male mice

Figure 5. Biochemical indexes of blood lipids in male wild-type and male Ldlr KO (em) mice. Mice were grouped and given different diets, and lipid metabolism indexes were measured at the 6^th, 8^th, 12^th, 16^th, and 20^th weeks of feeding. The results showed that compared to male wild-type mice (WT-M), male Ldlr KO mice (LDLR^-/--M) showed a slight increase in lipid levels under a common diet, while Ldlr KO mice were significantly elevated in all lipid indexes under high-fat diet (HFD). (CHOL: cholesterol; TRIG: triglycerides; HDL: high-density lipoprotein; LDL: low-density lipoprotein. The same as below.)

5. Biochemical indexes of blood lipids in female mice

Figure 6. Biochemical indexes of blood lipids in female wild-type and female Ldlr KO (em) mice. Mice were grouped and given different diets, and lipid metabolism indexes were measured at the 6^th, 8^th, 12^th, 16^th, and 20^th weeks of feeding. The results showed that compared to female wild-type mice (WT-F), female Ldlr KO mice (LDLR^-/--F) showed a slight increase in lipid levels under a common diet, while Ldlr KO mice were significantly elevated in all lipid indexes under high-fat diet (HFD). The results of this assay were identical to those of male Ldlr KO mice, indicating that a hyperlipidemic phenotype can occur in Ldlr KO mice of both sexes under a high-fat diet.

6. Aortic pathology

Figure 7. Detection of aortic plaque formation in wild-type mice and Ldlr KO (em) mice. Mice were grouped and given different diets and aortas were taken for observation at the 16^th week of feeding. Compared with other control groups, both male Ldlr KO mice in the G7 HFD and female Ldlr KO mice in the G8 HFD developed pathological plaques in the aorta, indicating that a high-fat diet can successfully induce the development of atherosclerosis in Ldlr KO mice. (G1: male WT mice + common diet; G2: female WT mice + common diet; G3: male WT mice + high-fat diet; G4: female WT mice + high-fat diet; G5: male Ldlr KO mice + common diet; G6: female Ldlr KO mice + common diet; G7: male Ldlr KO mice + high-fat diet; G8: female Ldlr KO mice + high-fat diet. Same as below.)

7. Progression of aortic plaque formation in Ldlr KO (em) mice

Figure 8. Detection of aortic plaque pathological process in Ldlr KO (em) mice. The observations of aortic plaque at different periods showed that aortic plaque formation was more pronounced in Ldlr KO mice fed high-fat for 20 weeks compared to mice fed high-fat for 16 weeks, and their plaque formation was further expanded. These changes were consistent with the trend in male and female mice.

8. Oil red O staining of the aortic arch in Ldlr KO (em) mice

Figure 9. Pathologic sections of the aorta in Ldlr KO (em) mice. Mice were grouped and given different diets and aortas were taken for observation at the 20^th week of feeding. Compared with other control groups, both male Ldlr KO mice in the G7 HFD and female Ldlr KO mice in the G8 HFD had thickening of the inner wall of the aorta, and lipid attachment occurred at the thickening part, indicating that a high-fat diet can successfully induce the development of atherosclerosis in Ldlr KO mice.

9. Summary

Ldlr KO mice were constructed by knockout of the Ldlr gene and induced hypercholesterolemia by high-fat diet feeding. The results showed that the model was characterized by hyperlipidemia and hypercholesterolemia, and the levels of blood lipid indexes such as CHOL, TRLG, LDL, and HDL of Ldlr KO mice were significantly increased after high-fat diet feeding compared with control mice. Ldlr KO (em) mice had thickening of the inner wall of the aorta and lipid attachment. Also, aortic plaque formation was present in this model after high-fat diet feeding, and the size and distribution of pathological plaques increased with the increase of high-fat feeding time.

In summary, Ldlr KO (em) mice can be used for the model of hypercholesterolemia, providing a strong and effective tool for the construction of the model of cardiovascular metabolic diseases and the study of related human diseases.

Ldlr KO (em) Mouse

基本情報

検証 Data

関連リソース

遺伝子名

遺伝子別名

NCBI ID

染色体

MGI ID

さらに

データシート

系統詳細

参考文献

系統作製戦略

適用分野

1. Protein expression

2. The growth curve

3. The growth curve

4. Biochemical indexes of blood lipids in male mice

5. Biochemical indexes of blood lipids in female mice

6. Aortic pathology

7. Progression of aortic plaque formation in Ldlr KO (em) mice

8. Oil red O staining of the aortic arch in Ldlr KO (em) mice

9. Summary

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