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AsianScientist (May 2, 2011) – Call it a mystery with a stubby tail: an odd-looking mouse discovered through a U.S. government breeding program in the 1940s that had a short, kinky tail and an extra set of ribs in its neck – and nobody knew why.
The ‘tail short’ mutant mouse first appeared in 1946 at the National Cancer Institute in Bethesda where several mutant mice were discovered among a litter of offspring born to a highly inbred strain of mice. They all had very unusual skeletal features: short, stubby tails and an extra set of ribs in their neck vertebrae.
It wasn’t just that the skeleton was malformed – it seemed to be misplaced. The neck vertebrae had ribs and resembled vertebrae lower in the spine. It appeared that the body plan of this mouse had been mixed up in early development.
Decades later, Dr. Maria Barna became interested in the mouse. She originally suspected that the mouse’s peculiar skeletal structures suggested some sort of anomalous “patterning” in early development, where one part of the body forms incorrectly in the shape of a different part.
Working with scientists at the National Institute of Genetics in Japan, the mutations unexpectedly turned out to be in the ribosome, a massive molecular machine that makes proteins and are common to all forms of life. Ribosomes are found in every cell in every organism – from carp to cholera.
As described in this week’s issue of the journal Cell, the mutations deleted a protein called Rpl38, one of 79 proteins that make up the mouse ribosome. Without Rpl38, the ribosome in the tail short mouse lost the ability to control which proteins it expressed. Moreover, the effect was not generalized throughout the body of the mouse, but specific only to certain tissues.
In early fetal development, the loss of Rpl38 caused certain parts of the backbone to grow and develop as if they were elsewhere in the spine – thus the extra ribs in the neck. Mutations in the proteins of human ribosomes can also lead to unexpected tissue-specific congenital birth defects including malformations of the spine, face, limbs, heart and other organs.
“The ribosome dictates where and when the final outcomes of gene products are expressed,” said Barna. “Therefore the genetic code has a previously unrecognized set of instructions that are carried out by the ribosome to control cell behavior. For example, whether or not a vertebrate has a pair of ribs associated with it.”
The work also suggests that ribosomes could act differently in different tissues in the body, adding an entirely new layer of complexity to the already complex program by which the genetic code is expressed in living creatures.
The article can be found at: Kondrashov N et al. (2011) Ribosome-Mediated Specificity in Hox mRNA Translation and Vertebrate Tissue Patterning.
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Source: University of California, San Francisco.
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