Application of anti-inositol metabolism medicament to establishment of mouse model with NTDs

A neural tube defect and mouse model technology, which is applied in the application field of anti-inositol metabolic drugs, can solve the problems of destroying genome structure, embryo weight loss, inositol deficiency, etc., and achieves low embryonic lethality and high rate of neural tube defects , less toxic and side effects

Inactive Publication Date: 2016-09-07
王建华
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] In addition to folic acid, perigestational inositol deficiency is closely related to the occurrence of NTDs. At present, it has not been successfully reported to directly establish an animal model of inositol deficiency by restricting food intake of inositol. Although Greene et al. It has been found that inositol deficiency can lead to stillbirth, growth retardation and weight loss of embryos, but NTDs and other birth defects have not appeared. This is because the nutritional status of the animal and the inositol diet Difficult to control, short-term lack of inositol, animals can use their own compensation mechanism to increase the synthesis of inositol in the body to meet the needs of the body
The use of gene knockout to construct animal models currently involves more than 200 related genes, but these NTDs models constructed using genetic engineering techniques tend to destroy the genome structure

Method used

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  • Application of anti-inositol metabolism medicament to establishment of mouse model with NTDs
  • Application of anti-inositol metabolism medicament to establishment of mouse model with NTDs
  • Application of anti-inositol metabolism medicament to establishment of mouse model with NTDs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Experimental Materials:

[0025] After adaptive feeding of 7-8 week-old SPF grade adult C57BL / 6J mice, female mice and male mice were caged overnight at a ratio of 1:1 or 2:1.

[0026] In the early morning of the next day, check whether there is a vaginal plug in the vaginal opening of the female rats. The presence of a vaginal plug indicates that there has been mating behavior. 8:00 the next morning when the vaginal plug is found is defined as 0.5 days of pregnancy (E0.5 days), and then the pregnant mice are pregnant. Raised in separate cages, randomly divided into experimental treatment group and control group.

[0027] At 7.5 days of pregnancy (E7.5 days), different doses (100mg / kg-400mg / kg) of Li 2 CO 3 After intraperitoneal injection, female mice in the normal control group were given an equal volume of normal saline.

[0028] On day 13.5 (E13.5 days) of pregnancy, the pregnant mice were plucked to collect blood from the eyes; the mice after blood collection wer...

Embodiment 2

[0045] With reference to Example 1, CD-1 pregnant mice were injected with Li2 CO 3 , below the dose of 300mg / kg body weight, no obvious toxic and side effects to pregnant mice were found. When the dosage was 350mg / kg body weight, toxic and side effects occurred in pregnant mice leading to a mortality rate of 13.3%, as shown in Table 4.

[0046] Table 4, different doses of Li 2 CO 3 Toxic and side effects on CD-1 pregnant mice

[0047] Dose (mg / kg body weight)

Number of pregnant mice injected

Number of deaths in pregnant mice

200

15

0

300

20

0

350

15

2

400

15

5

[0048] Table 5, 300mg / kg body weight dose Li 2 CO 3 Effects on neural tube defects

[0049] Dose (mg / kg body weight)

Absorbent ratio

incidence of neural tube defects

E8 day injection

30％

13％

[0050] Table 5 also proves that lithium salts can be used to construct a neural tube defect model, but compared wi...

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Abstract

The invention provides a method for obtaining a mouse model with neural tube defects (NTDs). The mouse model with the NTDs is established by applying an anti-inositol metabolism medicament to a pregnant mouse from the embryonic development of the pregnant mouse to the formation of neural tubes. The mouse model can be used for medical and biological research of the NTDs, is helpful to understand the causes and pathogenesis of human NTDs, and provides a model for further research on an action mechanism of inositol metabolic disorders in the NTDs. Moreover, according to the method, the neural tube defect rate is high, absorbed embryos are few, the embryo fatality rate is low, and toxic and side effects to the pregnant mouse are low.

Description

technical field [0001] The invention relates to a method for constructing a mouse model of neural tube defect, in particular to an application of an anti-inositol metabolism drug and a method for using the drug to construct a mouse model of neural tube defect. Background technique [0002] Neural Tube Defects (NTDs) refer to a group of birth defects caused by incomplete closure of the neural tube due to genetic predisposition and environmental factors in the early embryonic development. The main phenotypes include anencephaly, spina bifida and cerebral palsy. Meningocele or meningocele is the most common and serious congenital malformation of the central nervous system in fetuses and newborns, with a worldwide incidence of 0.05%-0.2%. NTDs are extremely harmful, such as anencephaly, fetuses with encephalocele and craniospina bifida are often stillborn or die soon after birth; children with spina bifida may survive, but they will cause neurological deficits, involving sensory...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K33/00
CPCA61K45/06A61K33/00
Inventor 王建华郭金石英飞王芳刘赛官臻王秀伟张霆牛勃安彦新
Owner 王建华
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