Unraveling Protein Misfolding Diseases Using Model Systems

Figures & data

Figure 1.  Model systems.

Shown clockwise from left, common laboratory mouse (Mus musculus), fruit fly (Drosophila melanogaster), zebrafish (Danio rerio), roundworm/nematode (Caenorhabditis elegans), baker's yeast (Saccharomyces cerevisiae) and bacteria (Escherischia coli).

Images obtained through Creative Commons license, with specific credit to the following: mouse, G. Shuklin; fly, Bbski; worm, kbradnam; bacteria, Rocky Mountain Laboratories.

Figure 2.  Organism-specific phenotypes resulting from protein aggregation.

Salient phenotypes arising from protein aggregation are described. In most cases severity scales with the amount or frequency of aggregation, allowing quantifiable assessment of physiological impact.

Table 1.  Comparison of model systems.

Organism	Generation time	Cost^†/day	Protocol required?	Time to generate gene knockout^‡
Mouse	3 months	1$ (per cage)	Yes	3–4 months
Zebrafish	3–4 months	0.6$ (per tank)	Yes	3–4 months (3–4 weeks kd^§)
Fruit fly	10 days	Negligible	No	1–3 months
Roundworm	4 days	Negligible	No	1–3 months (2–3 days kd^§)
Baker's yeast	90 min	Negligible	No	3–4 days
Bacteria	20 min	Negligible	No	3–4 fays

† All costs shown in US dollars.

‡ With extant mutant libraries, gene function can be immediately examined.

§ kd: Transient knockdown.