This document discusses the creation of the world's first transgenic dogs by a team in South Korea led by Byeong-Chun Lee. The dogs were created using somatic cell nuclear transfer to clone dog fibroblasts that had been infected with a virus inserting a fluorescent gene from sea anemones. This resulted in the birth of Ruppy, the first transgenic dog, and four others that glow red under UV light. The document outlines reasons for creating transgenic dogs, including using dogs as a model for studying inherited human diseases since dogs share 85% of the same genes as humans.
2. INTRODUCTION
• A TRANSGENIC ANIMAL IS AN ANIMAL "IN WHICH THERE HAS BEEN A DELIBERATE
MODIFICATION OF ITS GENOME, THE GENETIC MAKEUP OF AN ORGANISM
RESPONSIBLE FOR INHERITED CHARACTERISTICS," ACCORDING TO THE
FEDERATION OF EUROPEAN LABORATORY ANIMAL ASSOCIATIONS.
• A CLONED BEAGLE NAMED RUPPY – SHORT FOR RUBY PUPPY – IS THE WORLD’S
FIRST TRANSGENIC DOG. SHE AND FOUR OTHER BEAGLES ALL PRODUCE A
FLUORESCENT PROTEIN THAT GLOWS RED UNDER ULTRAVIOLET LIGHT.
3. BACKGROUND
• A TEAM LED BY BYEONG-CHUN LEE OF
SEOUL NATIONAL UNIVERSITY IN
SOUTH KOREA CREATED THE DOGS BY
CLONING FIBROBLAST CELLS THAT
EXPRESS A RED FLUORESCENT GENE
PRODUCED BY SEA
ANEMONES.[DRFP583]
• LEE AND STEM CELL RESEARCHER
WOO SUK HWANG WERE PART OF A
TEAM THAT CREATED THE FIRST
CLONED DOG, SNUPPY, IN 2005.
• SCIENTISTS HOPE TO KNOCK OUT A
SPECIFIC OESTROGEN RECEPTOR IN
DOGS TO UNDERSTAND THE
HORMONE EFFECTS ON FERTILITY
Fig-Ruppy the transgenic puppy at 10 days
old under ultraviolet light, showing the red
fluorescent protein produced by sea
anemones
4. MAKING A GLOWING DOG
• THE WORLD'S FIRST TRANSGENIC DOGS WERE PRODUCED BY SOMATIC CELL
NUCLEAR TRANSFER
• LEE’S TEAM CREATED RUPPY BY FIRST
INFECTING DOG FIBROBLAST CELLS WITH A
VIRUS THAT INSERTED THE FLUORESCENT
GENE INTO A CELL’S NUCLEUS.
• THEY THEN TRANSFERRED THE FIBROBLAST’S NUCLEUS TO ANOTHER DOG’S EGG
CELL, WITH ITS NUCLEUS REMOVED.
• AFTER A FEW HOURS DIVIDING IN A PETRI DISH, RESEARCHERS IMPLANTED THE
CLONED EMBRYO INTO A SURROGATE MOTHER.
5. WHY DOGS……
• THE DOMESTIC DOG, CANIS FAMILIARIS,
REPORTEDLY BEARS OVER 450 DISEASES;
APPROXIMATELY 360 OF WHICH ARE
ANALOGOUS TO HUMAN DISEASES
• HUMANS AND DOGS ARE 85 PERCENT
IDENTICAL GENETICALLY.
• AS A SPONTANEOUS MODEL FOR MANY
HERITABLE HUMAN DISEASES, THE DOG
PROVIDES AN EXCELLENT SYSTEM FOR THE
IDENTIFICATION AND STUDY OF DISEASE LOCI
, PARTICULARLY CANCER LOCI.
• SPECIFIC ADVANTAGES OF THE DOG SYSTEM
INCLUDE -A LIMITED NUMBER OF FOUNDERS,
POPULAR SIRES, LIMITED LOCUS AND DISEASE
HETEROGENEITY.
6. EXAMPLES
• INHERITED NEUROLOGICAL DISEASES HAS BEEN IDENTIFIED BY MEANS OF THE
DOG GENOME TO BE CAUSED BY A DODECAMER REPEAT IN THE EPM2B (NHLRC 1)
GENE THAT IS SAID TO BE RESPONSIBLE FOR IDIOPATHIC EPILEPTIC CASES.
• CARCINOGENIC PATHWAYS HAVE BEEN IDENTIFIED BY SCIENTIST BY USING THE
DOG GENOME TECHNIQUE TO ISOLATE AND IDENTIFY RCND MUTATION
RESPONSIBLE FOR RENAL CYSTADENOCARCINOMA AND DERMATOFIBROSIS
ESPECIALLY ASSOCIATED WITH GERMAN SHEPHERD DOGS.
• MAPPING STUDIES ARE UNDERWAY TO MAP CANCERS, KIDNEY DISEASES,
ENDOCRINE DISORDERS, BEHAVIORAL DISORDERS, EYE DISEASES AND
REPRODUCTIVE DISORDERS
7. DRAWBACKS
• USE OF A RETROVIRUS TO TRANSFER THE FLUORESCENT GENE INDICATING THEY
COULD NOT CONTROL WHERE THE VIRUS INSERTED THE GENE.
• IN THE FUTURE, CREATING A "KNOCKOUT" DOG, THE WAY RESEARCHERS DO
WITH MICE AND RATS, WOULD BE A CHALLENGE, AS WOULD "ENGINEERING DOGS
THAT PRODUCE MUTANT FORMS OF A GENE."
• LOW EFFICIENCY OF CLONING
8. REFERENCES
• GENERATION OF RED FLUORESCENT PROTEIN TRANSGENIC DOGS BY DAE YONG
KIM CHEMYONG KO AND BYEONG CHUN LEE
• THE DOG AS A MODEL ORGANISM FOR RESEARCH. - HANS ELLEGREN
• LEADING THE WAY: CANINE MODELS OF GENOMICS AND DISEASE BY ABIGAIL L. SHEARIN
AND ELAINE A. OSTRANDER
