Not too long ago, we told you about how California scientists discovered genes in sea squirts that might offer insights into Alzheimer’s disease. Now, there’s news of a similar genetic discover in the jellyfish-like, freshwater polyp known as Hydra. Both of these rudimentary organisms can now serve as easy-to-use research models for the debilitating disease, researchers say.
Bob Zeller, a developmental biologist at San Diego State University, was studying the nervous system of sea squirts — marine filter feeders also known as ascidians — when he found that a gene involved in the notch signaling pathway could also process the amyloid precursor protein, or APP, a key protein involved in Alzheimer’s disease in humans. “That got us thinking maybe we should look and see if there’s anything to it,” Zeller told Nature Medicine.
Zeller and his graduate student Mike Virata launched a bioinformatic search of the ascidian genome and discovered that sea squirts have all the genes needed to process APP in humans and other vertebrates. This was in stark contrast to other model invertebrates, such as fruit flies and nematode worms, which lack the gene encoding the enzyme beta-secretase — a integral component of the APP pathway. Thus, these stalwarts of the laboratory cannot form APP-related plaques, the hallmark of Alzheimer’s pathogenesis.
As we told you about earlier this month on the Spoonful of Medicine blog, the researchers inserted the human version of the APP protein into the sea squirts and observed plaques and behavioral defects within less than 24 hours. They then added a drug that is currently being tested in human clinical trials to reverse the effects of Alzheimer’s, and saw a reduced severity of plaques in the sea squirts. “That really got us excited,” says Zeller, who reported the findings in the May/June issue of the journal Disease Models & Mechanisms.
The easy-to-handle animals can now be used for drug screening in an intact organism within days — compared to mouse assays, which can take weeks, or human cell cultures, which won’t reveal subtle complexities.
Now, an international research team has also decoded the complete genetic blueprint of Hydra, a model experimental system for studying limb regeneration. In addition to findings about 20,000 protein-coding genes — a gene count in the same ballpark as the number found in humans — the researchers discovered genes linked with Huntington’s disease and with the beta-amyloid plaque formation seen in Alzheimer’s.
The genome sequence, which was published online yesterday in Nature, follows hot on the heels of the discovery of the tumor-causing gene myc in these 600-million-year-old metazoans. The deep ancestry of genes associated with cancer and neurodegeneration suggest that these diseases could be much older than previously thought.
Image of Hydra via Wikimedia
