Zebrafish Models of Batten Disease
Kim Wager, Courtesy of the
Laboratory of Claire Russell,
PhD, The Royal Veterinary
College, London, U.K.
Why do we need animal models of Batten’s
•To improve our understanding of the disease e.g. Which
brain cells are affected and why? What molecules are
involved in the disease?
•To develop and test new treatments e.g. To check that new
drugs are safe and what dose works best.
Why do we need Zebrafish models of Batten’s disease?
• Zebrafish can speed up drug discovery.
What makes Zebrafish a good model for
•Zebrafish are transparent. This means we can look inside
their brains while they are alive.
•The Zebrafish brain is surprisingly similar to human
•Their brain’s contain all the same types of cell as human
•The chemicals used by zebrafish brain cells are the same as
•Zebrafish develop external to the mother and very fast. This
means signs and symptoms progress very quickly.
•Zebrafish possess all the known Batten’s disease genes and
so can model all types.
The Zebrafish eye is a great tool to study
How are drugs tested on Zebrafish?
• Embryonic fish are laid out on a grid to which
candidate drugs can be added.
• Further experiments can then be carried out on the fish
to test if the drugs have had any effect.
• Do characteristics of the disease improve?
• Do the fish have an increased life span?
• Do any symptoms the fish have get better?
How do we test for Batten’s disease in
•Do lysosomes become enlarged?
•What storage material is present in the lysosomes?
•Are neurons dying; if so why?
•Do support cells (astrocytes) become activated?
•Do neurons get too excitable?
•Do the zebrafish suffer epileptic seizures?
•Is the blood brain barrier intact?
•Is there any inflammation in the brain?
•Are structures inside cells (e.g. mitochondria) working
Potential new drugs are
First these may be
tried on cell cultures
Zebrafish can be
used before mice,
they are cheaper
can then move on to
If the drug is safe
and seems to work,
human trials are
Safe, effective drugs
are brought to
Embryos are collected and
laid out on a grid so that we
know which fish have be
given specific drugs and
We can observe the
storage of unwanted
molecules in the
Brain cells and all
their interactions can
be observed in living
Credit: Dominik Paquet
Credit: Hideo Otsuna
Credit: Kara Cerveny