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Non-obese diabetic animal model and construction method and application thereof

A technology of animal models and diabetes, applied in biochemical equipment and methods, pharmaceutical formulations, compound screening/testing, etc., to achieve the effect of low cost, good stability and short cycle

Inactive Publication Date: 2019-10-25
HARBIN INST OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

NIK plays a key role in autoimmunity and acquired immune responses

Method used

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  • Non-obese diabetic animal model and construction method and application thereof
  • Non-obese diabetic animal model and construction method and application thereof
  • Non-obese diabetic animal model and construction method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0076] Example 1: Construction method of β-NIK-OE mice.

[0077] [Materials and Methods]:

[0078] Three strategies can be used to construct β-NIK-OE mice, namely:

[0079] (1) Set ROSA26Stop FL NIK mice were crossed with RIP-Cre mice (see figure 1 , A). ROSA26StopFL NIK mice are detailed in published articles (Ren X.et.al.FASEB J.2017; 31(2):711-718; LiX.et.al.Theranostics 2018; 8(21):5960-5971; Sasaki Y. et. al. PNAS 2008;105(31):10883-10888.). The details of rat insulin promoter Cre transgenic mice, namely RIP-Cre mice, can be found in published articles (Manuel BR et. al. Nat Commun. 2017; 8:16014.).

[0080] Such as figure 1 , shown in A, ROSA26Stop FL NIK mice are constructed with a stop sequence (STOP sequence) added between the two LoxP sites, and under normal circumstances there is no high expression of NIK. When ROSA26Stop FL After NIK mice are crossed with RIP-Cre mice (using the promoter of the rat insulin gene to control the expression of Cre enzyme, the ...

Embodiment 2

[0133] Example 2: Effects of β-NIK-OE on blood glucose in male mice.

[0134] The β-NIK-OE male mice obtained in Example 1 and the control mice (9 β-NIK-OE male mice, 11 control male mice, P<0.01), blood glucose was tested once a week (non-starvation state, 8:00-9:00 in the morning).

[0135] [Materials and Methods]:

[0136] β-NIK-OE (genotype: ROSA26Stop FL NIK + / + RIP-Cre + / - ) male mice and control mice (genotype: ROSA26Stop FL NIK + / + )

[0137] Blood glucose meter (ONETOUCH UltraEasy, Johnson & Johnson) and blood glucose test strips (ONETOUCH Ultra Steady, Johnson & Johnson)

[0138] [results see Figure 6 ]

[0139] [Result]: Compared with the control mice, all β-NIK-OE male mice began to increase blood sugar from the age of 5 weeks, the blood sugar reached 14mM at the age of 8 weeks, and maintained at about 20mM from the age of 9 weeks to 18 weeks .

Embodiment 3

[0140] Example 3: Effect of β-NIK-OE on blood glucose in female mice.

[0141] β-NIK-OE female mice and control mice were fed with normal diet (maintenance diet MD17121 for rats, Jiangsu Medison), and blood glucose was detected once a week (8:00-9:00 am in non-starvation state).

[0142] [Materials and Methods]:

[0143] β-NIK-OE (genotype: ROSA26Stop FL NIK + / + RIP-Cre + / - ) female mice and control female mice (genotype: ROSA26Stop FL NIK + / + )

[0144] Blood glucose meter (ONETOUCH UltraEasy, Johnson & Johnson) and blood glucose test strips (ONETOUCH Ultra Steady, Johnson & Johnson)

[0145] [results see Figure 7 ]

[0146] [Result]: Compared with the control mice, the blood sugar of β-NIK-OE female mice was slightly higher than that of the control female mice, and did not reach 14mM, and the β-NIK-OE female mice could not appear non-obese diabetes.

[0147] The present inventors have data showing that estrogen has an inhibitory effect on the development of diabete...

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Abstract

The invention provides a method of producing a non-obese diabetic (insulin-dependent diabetes mellitus) animal model. The method comprises overexpressing NIK (NF-kappa-B-inducing kinase) gene in pancreatic beta cells of an animal. Compared with existing non-obese diabetic (NOD) mouse models, beta-NIK-OE male mice herein have the advantages of good stability, short period, low expense and the like,and are applicable to the research on diabetic pathogenesis, the research on diabetic complications and the screening of diabetes drugs.

Description

technical field [0001] The invention relates to a method for producing an animal model of non-obese diabetes (also known as type 1 diabetes or insulin-dependent diabetes), which can be used for research on the pathogenesis of diabetes, research on diabetic complications and diabetes drug screening. Background technique [0002] Diabetes is one of the major diseases that threaten human health, and its important features are hyperglycemia and insulin secretion relative deficiency (type 2 diabetes or obesity diabetes or non-insulin-dependent diabetes) or absolute deficiency (type 1 diabetes or non-obesity diabetes or insulin-dependent diabetes mellitus). The incidence of type 2 diabetes in my country has reached 11.6%, and the incidence of type 1 diabetes is also increasing continuously. The country has invested more and more in basic research and drug development of diabetes. Research on the pathogenesis of diabetes and drug development requires a good diabetic mouse model. ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/85A01K67/027A61K49/00
CPCC12N15/8509C12N9/1205A01K67/0278A61K49/0008A01K2207/15A01K2217/05A01K2227/105A01K2267/0362
Inventor 陈政李新志鹿敏
Owner HARBIN INST OF TECH
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