Apr. 08, 2011

MicroRNAs Common to Three Lupus Mouse Models

Identification of a common lupus disease-associated microRNA expression pattern in three different murine models of lupus. 
Dai R, Zhang Y, Khan D, Heid B, Caudell D, Crasta O, and Ahmed SA. (2010). PLoS One 5: e14302.

What is the topic?
MicroRNAs are small pieces of genetic material. They are little bits of RNA, which is a substance that takes the blueprint for proteins from a person’s DNA and organizes the body’s ability to follow these instructions to make proteins. Specific blueprints in the DNA can be “turned off” by these microRNAs so that some proteins won’t be made.  

The role of microRNAs in lupus has recently been studied in mouse models of lupus. Each mouse model of lupus is made up of genetically identical mice that are specially bred in a laboratory. A problem in applying the information from mouse models to humans is that people with lupus are not genetically identical and the lupus itself is not always arising in the same way from one person to another because of this.  If common sets of microRNAs could be identified in different mouse models of lupus with different genetic backgrounds, then this would very likely increase their usefulness for the study of lupus in people.  

What did the researchers hope to learn?
The researchers hoped to identify a set of microRNAs common to three different strains of mice that have been genetically modified in different ways to have lupus, making it more likely that something similar to these microRNAs might be found in substantial percentages of people. 

Who was studied?
Three strains of lupus-prone mice were studied.

How was the study conducted?
Three strains of genetically lupus-prone female mice were studied and compared to healthy mice without lupus-like illness. Spleens were collected from the mice and then microRNAs and white blood cells (T cells and B cells), were isolated from them. Antibodies to anti-double-stranded DNA and protein from the kidney (an indication of lupus nephritis) were also studied. The microRNAs from the lupus-prone mice were tested to see which of them were present to a different degree (either higher or lower) than in mice without lupus.    

Six microRNAs from the genetically lupus-prone mice were studied using different methods to verify whether they were higher or lower than in mice without lupus.

What did the researchers find?
Preliminary studies looked at the mice at the age of 3-4 months. In two of the lupus mouse types, 15 of 617 possible microRNAs were found at levels different from those in normal mice without lupus. In the third lupus mouse strain, only one microRNA was found at different levels than in normal mice. 

Additional studies that compared lupus prone and normal mice aged 3, 4, and 9 months showed that four microRNAs from the spleens were found at different levels in all three lupus-prone mouse strains compared to normal mice. In addition, as the mice got older, the levels of antibodies to anti-double-stranded DNA were significantly higher in two of the three lupus-prone mice than in normal mice. 

What were the limitations of the study?
Differences in levels of microRNAs and anti-double-stranded DNA antibodies were difficult to detect in one of the three mouse strains used in this study. Although this makes it less likely that the findings apply to most people with lupus, it could help to identify subsets of lupus patients who could be studied to see what happens to them or to which treatments they respond best. In this way, the microRNA approach could become a diagnostic test that could be used to identify people for optimal treatment approaches. Also, two of the mouse strains used in this study are also used as models of other autoimmune diseases, such as rheumatoid arthritis and Sjögren’s syndrome. Therefore, it will be important to determine whether the microRNA changes seen here are important to lupus or not.    

What do the results mean for you?
If verified in human studies, certain patterns of microRNA changes that might have first been identified in lupus-prone mice might one day be used to sort out people with lupus who need monitoring for specific risks, to help pick optimal treatments, guide the dosing of some treatments, and serve as early predictors of responsiveness to treatment. However, much more work needs to be done before that can become a reality.


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