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Animal Models: Sheep, cattle and horses with NCL
Imke Tammen, Peter J. Houweling & Izmira F. Mohd Ismail, Faculty of Veterinary Science,
The University of Sydney, Australia ([email protected]) and Batten Animal Research Network (BARN)
INTRODUCTION
PAST RESEARCH HIGHLIGHTS
Large animal models for Batten
disease enable research towards a
better understanding of the
disease mechanisms and are
important for the evaluation of
therapeutic approaches in
preclinical trials.
•Establishment of the NCL Merino research flock
•Identification of the mutations causing the CLN6 form in
South Hampshire sheep and a different CLN6 form in
Australian Merinos
•Identification of the mutations causing CLN5 in Devon cattle
Over the last decade researchers
in Australia (1) and New Zealand
have been working on Batten
disease, using flocks of sheep (2)
to study aspects of the human
diseases, and we have integrated
our activities through the
formation of the Batten Animal
Research Network (BARN).
CURRENT PROJECTS
A) Molecular characterisation of NCL in horses.
B) Development of non-invasive methods to determine preclinical pathology in Merino sheep, to allow monitoring of the
efficacy of treatments under trial (3-5).
1
3
4
1. The Australian BARN team: Imke (left)
and past and current PhD students Peter
(middle) and Izmira (right)
2
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3-5. Magnetic resonance imaging (3) and behavioural studies (4&5) in
Australian Merino sheep with NCL for the development of longitudinal in
vivo markers for disease progression.
2. The Australian NCL Merino
research flock
WHAT THIS MEANS
FOR THERAPY
1. The identification of the
disease causing genes
and mutations in these
animal models allows
preclinical diagnosis
from conception and us
to match an animal
model to the
corresponding human
NCL
2. Therapeutic approaches
(e.g. pharmaceuticals,
gene and stem cell
therapies) need to be
evaluated for safety and
efficiency. The use of
both small and large
animal models is
recommended before
clinical trials in humans
commence.
3. To assess the efficiency
of therapeutic
approaches in animals
we need to have a
range of measures of
disease progression
over time – MRI and
behavior measures
appear to be useful in
this context.
Acknowledgements:
Technical support by D. Palmer and G. Attard as well as
the support of honours students (D. Beganovic, N.
Foreman, B. Lui, H. Okazaki, A. Sutton & E. Wan) and
colleagues (G. Cronin, A. Hollmann, K. Hughes, E. Jonas,
M. Makara, P. Thomson, C. Wade, C. Willet & S. Zaki) is
acknowledged.