Methods of modulating apoptosis by administration of relaxin agonists or antagonists

a technology of relaxin and agonists, which is applied in the direction of hormone peptides, drug compositions, peptide/protein ingredients, etc., can solve the problems of increasing collagen deposition, reducing and affecting the development of various body tissues. , to achieve the effect of increasing or decreasing the functional activity of molecul

Inactive Publication Date: 2005-02-10
MOLECULAR MEDICINE RES INST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The term “relaxin analog” refers to a modified relaxin polypeptide that increases or decr

Problems solved by technology

Knockouts of the gene encoding relaxin result in various abnormalities in the development of various body tissues, including smaller size of, incre

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

The effect of inactivation of one or both alleles of the mouse RLX genes was examined. The following methods and materials were followed.

Animals:

Wild-type, heterozygous and homozygous relaxin knockout mice were obtained from the Howard Florey Institute of Experimental Physiology and Medicine (Parkville, Victoria, 3052, Australia) and used to establish a breeding program. Subsequent generations of RLX + / + (wild-type), RLX + / − (heterozygous) and rlx − / − (null mutant) mice were generated from RLX + / − parents. All animals were housed in a controlled environment and maintained on a 14 hours light, 10 hours dark schedule with access to Labdiet rodent lab chow (Deans Animal Feed, San Bruno, Calif.) and water. These experiments were approved by the Institute's Animal Experimental Ethics Committee, which adheres to the NIH Code of Practice for the care and use of laboratory animals.

Genotyping by PCR

Mouse DNA was isolated by lysing tail tissue (5-7 millimeters) in 400 μl of PCR lysis...

example 2

The Effects of Relaxin Gene Knockout on the Growth of Mice:

The body weights of male and female relaxin wildtype (+ / +), heterozygous (+ / −) and null mutant (− / −) mice were measured at 1 week, 1 month, 2 months and 3 months of age (n=20-21 for each group). No significant differences in mean body weight were noted in male (RLX + / +: 3.87±0.09 g; rlx − / −: 3.6±0.13 g) or female (RLX + / +: 3.52±0.09 g; rlx − / −: 3.37±0.08 g) mice at 1 week of age. However, at the time the mice were 1 month of age, mean body weights of both rlx − / − males (17.05±0.65 g) and females (14.77±0.42 g) were significantly less (p<0.05) than their respective RLX wildtype counterparts (RLX + / + M: 18.92±0.61g; RLX + / + F: 16.34±0.51 g). Male and female null mutant mice continued to be significantly smaller (p<0.05) than RLX wildtype animals at 2 months of age (RLX + / + M: 25.42±0.41 g; rlx − / − M: 24.23±0.42 g; RLX + / + F: 20.96±0.32 g; rlx − / − F: 19.94±0.22 g); however, the differences in size between the two g...

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Abstract

The present invention relates to the discovery that relaxin is associated with the development or maturation of body tissues. Knockouts of the gene encoding relaxin result in various abnormalities in the development of various tissues. The present invention provides methods of modulating apoptosis by administering a relaxin agonist or antagonist to a subject.

Description

BACKGROUND OF THE INVENTION The growth and development of normal tissues is achieved by programmed cell proliferation, differentiation and cell death. Cell proliferation and differentiation are required for the formation of new cells and tissues. Conversely, programmed cell death, also referred to as apoptosis, is required to remove existing cells, including immature or damaged cells. Apoptosis naturally occurs in virtually all tissues of the body. Apoptosis plays a critical role in tissue homeostasis, that is, it ensures that the number of new cells produced are correspondingly offset by an equal number of cells that die. For example, the cells in the intestinal lining divide so rapidly that the body must eliminate cells after only three days in order to prevent the overgrowth of the intestinal lining. The disruption of the genetic program, by either abnormally increasing or decreasing rate of cell proliferation and / or apoptosis can result in abnormal tissue development. For exam...

Claims

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Application Information

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IPC IPC(8): A61K38/22
CPCA01K67/0276C07K14/64A61K38/2221A01K2227/105A61K38/22A61P1/00A61P1/16A61P5/00A61P9/00A61P11/00A61P13/08A61P13/12A61P15/00A61P25/00A61P35/00A61P43/00
Inventor AMENTO, EDWARD P.SAMUEL, CHRISHAN S.
Owner MOLECULAR MEDICINE RES INST
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