EDEMA – A SIGN OF UNDERLYING DEVELOPMENTAL DEFECTS


In around 30% of the knockout lines studied by DMDD, the embryos have edema – swelling due to fluid trapped in the embryo’s tissues. Most of us have experienced edema at some point, after a bee sting, an infection or perhaps from hitting your thumb with a hammer. One reason that it happens is if small blood vessels start to leak, releasing fluid into the surrounding tissue. And in some cases it can be helpful – for example the additional white blood cells in the fluid can help fight infection more quickly.

In embryos from our embryonic lethal knockout lines, however, edema is more generalised, often surrounding the brain, abdomen or the entire body. We spot it in the initial checks of the embryo, where we look for major abnormalities that are visible without detailed imaging. In the image below, a Traf6 knockout embryo clearly shows edema around the skull and back.

A Traf6 homozygous knockout embryo shows edema around the back of the skull and body.

 

In adult humans, we know that more generalised edema can be caused by heart failure. If the heart is not able to pump blood around the body quickly enough then fluid can build up in the legs, lungs and abdomen. It can also be caused by liver and kidney diseases, as well as many other critical conditions.

The equivalent phenotype in human foetuses is known as hydrops fetalis. It’s an excessive accumulation of fluid in the body cavities, and can have a root cause in the foetus itself, in the placenta or in the mother. It’s the end stage of many different disorders. [1]

 

It’s almost never the edema that kills, but the underlying etiology. (Dr Fowzan Alkuraya, King Faisal Hospital, Riyadh).

 

The edema we see in embryonic lethal knockout mice is therefore unlikely to be a direct cause of lethality. As we might expect, many DMDD embryos with edema also show a wide range of other abnormalities, like this Ssr2 knockout that has a ventricular septal defect as well as subcutaneous edema.

 

Click to view larger image.

An Ssr2 knockout embryo has a ventricular septal defect as well as subcutaneous edema.

 

So when we see this general type of edema in our initial checks, it’s a huge clue that there may be serious underlying abnormalities that have led to the embryo’s demise. And to identify these we need detailed imaging.

[1] C. Bellini et al., Etiology of non-immune fetal hydrops: a systematic review, Am Gen Med Genet A, 149A (2009) p844-851.

 


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