Presented by Mingyan Yu, Charity Muteti, Moses Ogugo and Steve Kemp at the ILRI BioSciences Day, Nairobi, 27 November 2013

1. Transgenic approach to improved productivity:
Establishing African Trypanosomiasis resistance in cattle by a
transgenic approach
Mingyan Yu, Charity Muteti, Moses Ogugo, Steve Kemp
Animal Biosciences, ILRI
ILRI BioSciences Day, Nairobi, 27 November 2013
Partner go
New York University
Roslin Institute/ University of Edinburgh
Michigan State University

2. The problem
African Trypanosomiasis
• Caused by extracellular protozoan
parasites – Trypanosoma
• Transmitted between mammals by
Tsetse flies (Glossina sp.)
• Prevalent in 36 countries of subSahara Africa.
http://www.imib-wuerzburg.de/research/siegel/research/
Trypanosomes in Blood stream
In cattle
• A chronic debilitating and fatal
disease.
• A major constraint on livestock and
agricultural production in Africa.
• Costs US$ 1 billion annually.
In human (Human Sleeping Sickness)
• Fatal
• 60,000 people die every year
• Both wild and domestic animals are
the major reservoir of the parasites for
human infection.
http://www.bio.davidson.edu/courses/immunology/students/spring2006/ryan/termpaper.html

3. The problem
Vector Control (Tsetse Fly)
• Using toxic insecticide
• Negative impacts on environment
• Not sustainable
• Expensive
Vaccine
• Tryps periodically change the major surface antigen – variant
surface glycoprotein (VSG) and evade the host immune system.
• More than 2 decades, there is no effective vaccine developed.
Drug
• No prophylactic drugs
• Drug toxicity and resistance
• Expensive
New idea

4. Establish African Trypanosomiasis Resistance in Cattle by A
Transgenic Approach
• Establish a transgenic cattle model with African
Trypanosomiasis resistance using nuclear transfer (cloning).
• On the background of a Kenyan indigenous breed – Kenyan
Boran.
• Introduce the gene – apoL-I from Baboon into Boran, which is
the key trypanolytic component of Baboon’s protective
Trypanosome Lytic Factor (TLF) against both cattle and humaninfective trypanosomes.

5. Innovation in the work
• Using a transgenic approach to create disease
resistance in cattle
• The method is once for all and self-sustainable
- Once the resistance is established, it could be transmitted to the
next generations through normal breeding.

6. Links to ILRI’s SO and CGIAR SLO
Tryps Resistant Cow
Delivery partners needed
ILRI SO:
Better lives
through livestock
Small-scale
Farmers
Improved livestock productivity
More meat and
milk
More income
from sales
SLO3
Improve nutrition
and health
Improved crop
productivity
SLO2
Improve food
security
CRP 3.7 –
Genetic
component
SLO1
Reduce rural
poverty
CGIAR System Level Outcomes
6

7. Importance to ILRI
•
Improved capacity with new technology
(cloning) platform
•
Being the lead in transgenic livestock research
in Africa (challenge & opportunity)
•
Improved public visibility and image by
resolving the persistent trypanosomiasis
problem
7

8. Project Process
Kenya
Boran
Genomic locus of
Baboon apoL-I gene
Vector construction
ILRI
Bovine embryonic fibroblasts
(BEF) primary culture
Roslin
Institute
Validate the construct in
transgenic mouse
Transfection & screening
apoL-I Transgenic BEFs
(male)
Nuclear Transfer
ILRI
(cloning)
Transgenic calves
Phenotyping
Trypanosome resistant
transgenic Boran bull
New York
University
Michigan
State
University

9. Results
Two Cloned Calves born through Caesarean Section
ID: Tatu
Date of Birth: 16 July 2012 (Kapiti)
Sex: Male
Birth Weight: 46 kg
Date of Death: 19 July 2012 (74 hrs)
Cause of death: Low temperature,
low blood glucose …
ID: CL001 (Tumaini)
Date of Birth: 21 August 2012 (ILRI)
Sex: Male
Birth Weight: 35 kg
Current age: 15 months, healthy

10. 15-Month
At Birth
CL001 (Tumaini)

11. Fund & Partnership
This work is funded by
US National Science Foundation
&
BREAD Program
RDA-ILRI Fund
(Korean)
It is implemented in a partnership with
New York University
Michigan State University
Roslin Institute, University of Edinburgh

12. Where to from now?
Current Project
Potential Future Projects
Transfection of Boran BEFs line
(Roslin Institute, UK)
Biosafety Research
• Confirm no health risk of the
gene to the transgenic cow
• Confirm the safety of meat and
milk consumption of the apoL1
transgenic cow
Establish Apol-I Transgenic Boran by
nuclear Transfer with Transgenic Cells
Phenotyping (confirm Tryps resistance)
• ApoL-I expression pattern
• Killing of Trypanosomes in vitro
(serum) and in vivo (challenge)
• Monitor the health conditions with
growth
Increase Genetic Diversity
• Establish more transgenic cattle
with Kenya Boran BEFs lines
• Establish transgenic cattle with
other Kenyan indigenous breeds
Transgene Delivery
• Develop a breeding programme
to disseminate the transgene to
farmers

13. Potential opportunities
More application of established cloning platform
• Improve cattle genetics through traits introduction
between breeds
- Using TALENs and cloning together to introduce good traits between
breeds to obtain efficient cross-breeding.
• Indigenous breeds conservation
- Establish a bank of cells from indigenous breeds of cattle, sheep and
goats, which are capable of cloning.
• Training for other African regions
- Make good use of the technique to maintain the best animal genetics
and improve the livestock productivity in Africa.

14. General discussion (facultative)
Resource mobilization strategy
• Trypanoresistant cow project – wait and see
• Traits introduction between breeds using TALENs seeking collaboration and new traits
What support do you expect from ILRI and the
BioScience Directorate?
• Effective communications with the public regarding
the transgenic cow project in due course.

15. better lives through livestock
ilri.org
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