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After writing a research paper on frame for one of my college classes, I can now better explain exactly why frame is lethal.

Warning: lots of genetic and scientific language ahead and potentially upsetting descriptions of cause of death (I’ll try not to get into too much detail on that part)

As I mentioned in Frame in Real Life, a hom frame foal dies because the nerves in its intestines don’t develop and the foal can’t poop. Here’s a little more insight into exactly why that happens.

The genetic mutation that causes frame overo occurs in the endothelin B receptor gene (EDNRB gene). This gene is crucial during embryonic development because it tells certain cells that they need to migrate to the intestines and develop into the type of nerve cell that allows the intestines to contract and push out waste.

The frame mutation changes the gene’s sequence so it can’t function properly. At Residue 118 (residues are basically locations on the protein chain within the gene) of the EDNRB gene, the amino acid isoleucine is the amino acid that should be there. However, the frame overo mutation replaces the isoleucine at Residue 118 with another amino acid called lysine.

This one tiny change completely changes the gene’s sequence. Because of the change, the EDNRB gene can’t tell the cells where they need to go and what type of cell they need to become, so those nerve cells just never develop.

Heterozygous frame horses survive because they still have one non mutated EDNRB gene that can function to create enough of the necessary cells.

Potentially upsetting content

Without these intestinal nerve cells, the foal’s intestines can’t contract, so the foal can’t poop. As the foal continues to nurse, it continues to produce waste that its body is unable to expel. This causes the foal to experience severe abdominal pain that cannot be relieved. Eventually, enough waste builds up to rupture the intestines. The foal either dies from shock caused by contamination of its internal organs or from sepsis.

End of potentially upsetting content

I hope this has helped some people learn more about exactly why homozygous frame is lethal!