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Trypanosomes live and multiplyextracellularly in blood and tissue fluidsDistribution corresponds to the distribution of Tsetse flies – tsetse beltAlso a threaten for human.
Antigenic variation is transcriptional switching from one VSG gene to another.There are no prophylactic drugsNew idea for a sustainable way to control the disease
TLF only exists in primates. Gain resistance during evolution. Baboon is remarkably resistant to both animal and human infective species.Cattle also has the family of apoL, but no apoL1. Previous research with transgenic mice proved that baboon apoL-1 expression in mice can protect the mice from the tryps infection. We hypothesize that expression of baboon apoL-1 in cattle can protect cattle in the same way.
Cloning is a technology widely used in the developed countries that allows livestock breeders to create identical twins of their best animals and ensure that the herds are maintained at the highest quality and most productive level.
11 BEFs cell lines were isolated, 6 female and 5 male. If it works, we could have more genetic diversity using different cells lines to make transgenic cows.We prefer male BEFs, because it is more efficient to spread the transgene in the cattle.To test the technique and suitability of Boran for cloning, we tried cloning using original BEFs without transgene.
Once the cloned animal survives, they are normal and can breed naturally.
Transgenic approach to improved productivity: Establishing African Trypanosomiasis resistance in cattle by a transgenic approach
Transgenic approach to improved productivity:
Establishing African Trypanosomiasis resistance in cattle by a
Mingyan Yu, Charity Muteti, Moses Ogugo, Steve Kemp
Animal Biosciences, ILRI
ILRI BioSciences Day, Nairobi, 27 November 2013
New York University
Roslin Institute/ University of Edinburgh
Michigan State University
• Caused by extracellular protozoan
parasites – Trypanosoma
• Transmitted between mammals by
Tsetse flies (Glossina sp.)
• Prevalent in 36 countries of subSahara Africa.
Trypanosomes in Blood stream
• A chronic debilitating and fatal
• A major constraint on livestock and
agricultural production in Africa.
• Costs US$ 1 billion annually.
In human (Human Sleeping Sickness)
• 60,000 people die every year
• Both wild and domestic animals are
the major reservoir of the parasites for
Vector Control (Tsetse Fly)
• Using toxic insecticide
• Negative impacts on environment
• Not sustainable
• 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.
• No prophylactic drugs
• Drug toxicity and resistance
Establish African Trypanosomiasis Resistance in Cattle by A
• Establish a transgenic cattle model with African
Trypanosomiasis resistance using nuclear transfer (cloning).
• On the background of a Kenyan indigenous breed – Kenyan
• 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.
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.
Links to ILRI’s SO and CGIAR SLO
Tryps Resistant Cow
Delivery partners needed
Improved livestock productivity
More meat and
CRP 3.7 –
CGIAR System Level Outcomes
Importance to ILRI
Improved capacity with new technology
Being the lead in transgenic livestock research
in Africa (challenge & opportunity)
Improved public visibility and image by
resolving the persistent trypanosomiasis
Genomic locus of
Baboon apoL-I gene
Bovine embryonic fibroblasts
(BEF) primary culture
Validate the construct in
Transfection & screening
apoL-I Transgenic BEFs
transgenic Boran bull
Two Cloned Calves born through Caesarean Section
Date of Birth: 16 July 2012 (Kapiti)
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)
Birth Weight: 35 kg
Current age: 15 months, healthy
Fund & Partnership
This work is funded by
US National Science Foundation
It is implemented in a partnership with
New York University
Michigan State University
Roslin Institute, University of Edinburgh
Where to from now?
Potential Future Projects
Transfection of Boran BEFs line
(Roslin Institute, UK)
• Confirm no health risk of the
gene to the transgenic cow
• Confirm the safety of meat and
milk consumption of the apoL1
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
Increase Genetic Diversity
• Establish more transgenic cattle
with Kenya Boran BEFs lines
• Establish transgenic cattle with
other Kenyan indigenous breeds
• Develop a breeding programme
to disseminate the transgene to
More application of established cloning platform
• Improve cattle genetics through traits introduction
- 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.
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
• Effective communications with the public regarding
the transgenic cow project in due course.
better lives through livestock
The presentation has a Creative Commons licence. You are free to re-use or distribute this work, provided credit is given to ILRI.
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