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Steatohepatitis-liver cancer model animal

Inactive Publication Date: 2012-05-10
STELIC INST OF REGENERATIVE MEDICINE STELIC INST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0021]As described above, the present inventors successfully produced model animals for steatohepatitis and liver cancer which show similar pathological findings to those of human, and thereby completed the present invention. By using these model animals, it is possible to efficiently screen for substances for treating or preventing diseases, and effectively evaluate the efficacy of medicinal substances.
[0057]The present invention provides simple techniques for stably producing animals that develop at an early stage a pathological condition similar to human NASH, which leads to fatty liver, steatohepatitis, hepatic fibrosis, and liver cirrhosis, followed by spontaneous development of liver cancer as a result of progression of the pathological condition, by inducing insulin resistance in experimental animals such as mice, and loading them with a high fat diet.

Problems solved by technology

However, it was revealed that even non-drinkers develop inflammation similar to alcoholic hepatitis and show hepatic fibrosis histology, and now the non-alcoholic fatty liver disease is known as a disease with poor prognosis.
However, the mechanism remains unclear, and effective methods and / or agents for treating NASH have not been established.
This is partly because NASH is due to human lifestyle-related diseases, and thus appropriate experimental animals have not been established.
Furthermore, insulin resistance and hepatic fibrosis cannot be simultaneously monitored in these mice.
This makes it difficult to test and assess drugs for their efficacy.
Although various studies have been conducted, there is no experimental animal exhibiting pathological conditions similar to those of human.
Thus, under the current circumstances, it is difficult to conduct detailed screening to elucidate the pathogenesis or to establish therapeutic methods.

Method used

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  • Steatohepatitis-liver cancer model animal
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  • Steatohepatitis-liver cancer model animal

Examples

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example 1

Preparation of NASH Model Animals and Liver Cancer Model Animals

(a) Preparation of NASH Model Mice

[0140]Gestational C57BL6J / JJcl, C3H / HeNJcl, and BALB / cByJJcl (CLEA Japan Inc.) and C57BL6J / NCrlCrlj (Charles River Japan, Inc.) were reared and allowed to deliver. Pancreatic inflammation was induced in male mice of C57BL6J / JcL, BALB / cByJJcl, and C3H / HeNJcl (CLEA Japan Inc.) two days after birth with cytotoxicity specific to N-Acetyl-beta-D-glucosaminidase (O-GlcNAcase) in pancreatic β cells (for example, by subcutaneously administering 10 mg / ml streptozotocin (SIGMA) at 20 μl / head). Thus, insulin resistance was induced by directly or indirectly eliciting inflammation in peripheral tissues. The mice were reared with a CE-2 diet (CLEA Japan Inc.) and sterile water until four weeks old, and ablactated when they reached the age of four weeks. Then, the mice were reared until 20 weeks old with sterile water and High Fat Diet (CLEA Japan Inc.) or D12492 (Research Diets), which have a higher ...

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Abstract

Fatty liver was induced by administering agents for inducing organ inflammation to experimental animals to evoke insulin resistance and by rearing them with high-fat diets. As a result, steatohepatitis was successfully induced in the animals. The animals show pathological findings similar to those of humans. By using these model animals, substances for treating or preventing diseases can be efficiently screened and the efficacy of medicinal substances can be effectively evaluated.

Description

TECHNICAL FIELD[0001]The present invention relates to steatohepatitis / liver cancer model animals, and uses thereof.BACKGROUND ART[0002]Previously, non-alcoholic fatty liver disease was believed to be a benign disease that does not progress. However, it was revealed that even non-drinkers develop inflammation similar to alcoholic hepatitis and show hepatic fibrosis histology, and now the non-alcoholic fatty liver disease is known as a disease with poor prognosis. In particular, metabolic syndromes due to obesity, diabetes, or the like have been drawing attention in recent years. It is becoming a common view that nonalcoholic steatohepatitis (NASH) is one of such syndromes. However, the mechanism remains unclear, and effective methods and / or agents for treating NASH have not been established. This is partly because NASH is due to human lifestyle-related diseases, and thus appropriate experimental animals have not been established.[0003]For the development of effective methods and agen...

Claims

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Application Information

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IPC IPC(8): A01K67/027G01N33/566C12Q1/02A61K49/00A61K31/7008
CPCA01K67/027A01K2207/20A01K2267/0331A01K2227/10A01K2207/25
Inventor YONEYAMA, HIROYUKIFUJII, MASATO
Owner STELIC INST OF REGENERATIVE MEDICINE STELIC INST
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