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Applications of MEN1 gene and encoding protein thereof

A gene and coding technology, which is applied in the field of preparation and screening of drugs for the treatment of liver fibrosis and fatty liver, can solve problems such as translation errors, loss of protein expression, and staying in the primary stage.

Active Publication Date: 2013-08-21
SHANGHAI INST FOR ENDOCRINE & METABOLIC DISEASES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, thousands of MEN1 gene mutation sites have been identified, all over the coding region and promoter of the MEN1 gene, resulting in loss of protein expression or translation errors, resulting in the loss of the tumor suppressor function of menin and the occurrence of tumors
However, the structure of menin is relatively special, and no motif (mortif) consistent or similar to any known protein has been found
Therefore, the current understanding of the specific molecular mechanism of menin as a tumor suppressor gene to regulate gene transcription is still in its infancy, and whether menin has other important biological functions besides tumor suppressor remains to be explored

Method used

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  • Applications of MEN1 gene and encoding protein thereof
  • Applications of MEN1 gene and encoding protein thereof
  • Applications of MEN1 gene and encoding protein thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Example 1 Establishment of Liver-specific MEN1 Gene Knockout Mouse Model (LMKO)

[0038] A liver-specific MEN1 gene knockout (Liver-Specific Menin Knockout, LMKO) mouse model was established by the following steps using the Cre / LoxP strategy

[0039] 1) Obtain Cre recombinase transgenic mice (Alb-Cre+) driven by the promoter of albumin gene from Nanjing Model Animal Center.

[0040] 2) Transgenic mice (MEN1loxP / loxP) constructed with LoxP sites at both ends of the MEN1 locus (Locus) were obtained from Jackson Lab.

[0041] 3) Male Alb-Cre+ and female MEN1loxP / loxP mice were crossed, and F1 generation heterozygous mice (Alb-Cre+; MEN1loxP / -) were screened.

[0042] 4) Cross male heterozygous mice (Alb-Cre+; MEN1loxP / -) with female MEN1loxP / loxP, and finally screen to obtain pure and LMKO mice (Alb-Cre+; MEN1loxP / loxP) and corresponding normal controls (Alb- Cre-; MEN1loxP / loxP).

[0043] Through PCR genotyping and immunohistochemical analysis of liver tissue sections,...

Embodiment 2

[0045] (1) Establishment of mouse liver fibrosis model

[0046] Adult mice aged 8-10 weeks were selected and divided into 4 groups with 10 mice in each group, namely: wild-type control group, knockout control group, wild-type liver fibrosis experiment group, and knockout liver fibrosis experiment group. group, wild-type liver cirrhosis experimental group, and knockout liver cirrhosis experimental group. The experimental group was injected intraperitoneally with 0.5 mL / kg of CCl4 (dissolved in olive oil at a ratio of 1:7, and then injected 10 uL of drug per gram of body weight according to the weight of the mice), and the control group was injected intraperitoneally with the same amount of olive oil for 2 days a week. Each time, a total of 4 weeks and 8 weeks were injected to establish animal models of liver fibrosis and cirrhosis in mice, respectively.

[0047] (2) The role of MEN1 gene in the liver

[0048] In order to explore the role of the MEN1 gene in the liver, we harv...

Embodiment 3

[0069] (1) Establishment of mouse hyperlipidemia model

[0070] Select 6-8 week-old mice, 12 in each of the control group and the knockout group, and feed them with high-fat diet (containing 60% fat) for 12 weeks to establish a high-fat obesity mouse model.

[0071] (2) The expression of Menin is down-regulated in the liver and fat of db / db mice

[0072] Menin protein levels were significantly downregulated in the liver and adipose tissue of the type 2 diabetes db / db mouse model compared with control wild-type mice. However, the expression of menin in muscle tissue did not change significantly. Such as Figure 8 shown.

[0073](3) Loss of MEN1 expression in hepatocytes does not affect lipid metabolism under normal diet

[0074] In order to study the effect of MEN1 gene on lipid metabolism, we first established hepatocyte-specific MEN1 gene knockout (Alb-Cre+; MEN1loxP / loxP, namely LMKO) and normal control group (Alb-Cre - ; MEN1loxP / loxP, that is, WT) mouse model, fed wit...

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Abstract

The invention relates to the field of medicine biology, wherein a liver-specific MEN1 gene knocked out mouse model is established to research effects of menin in liver cells, and results show that MEN1 gene provides important effects in EMT inhibition (epithelial-mesenchymal transition of liver cells) and glycolipid metabolism regulation. In addition, the MEN1 gene can be adopted for preparing and screening anti-hepatic fibrosis and anti-fatty liver drugs so as to provide valuable clues and directions for clinical targeted therapy.

Description

technical field [0001] The invention belongs to the field of medical biology, and relates to the application of MEN1 gene and its coded protein in the preparation and screening of drugs for treating liver fibrosis and fatty liver. Background technique [0002] In 1997, Chandrasekharappa et al. first identified and cloned a new tumor suppressor gene, MEN1, in the third band (11q13) of the long arm of human chromosome 11. The protein menin encoded by this gene is an endocrine tumor suppressor factor present in various tissues and cells. Its deletion or mutation induces a relatively rare autosomal dominant genetic disorder, multiple endocrine neoplasia type 1, which causes a variety of endocrine neoplasms including parathyroid tumors, pancreatic islet cell tumors, and pituitary tumors2 . At present, thousands of MEN1 gene mutation sites have been identified, all over the coding region and promoter of MEN1 gene, resulting in loss of protein expression or translation errors, re...

Claims

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Application Information

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IPC IPC(8): A61K48/00A61K38/17A61P1/16C12Q1/68G01N33/68
Inventor 宁光薛璐李小英刘瑞欣姜秀丽曹亚南
Owner SHANGHAI INST FOR ENDOCRINE & METABOLIC DISEASES
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