Growth Hormone (GH)mcb.berkeley.edu/courses/mcb41/lecture_17.pdfReview of recombinant DNA technology...
Transcript of Growth Hormone (GH)mcb.berkeley.edu/courses/mcb41/lecture_17.pdfReview of recombinant DNA technology...
Transgenic organisms or
Genetically ModifiedOrganisms (GMOs)
Review of recombinant DNA technology
Growth Hormone
Reading for this and next lecture: Chapter 19
GAATTC
CTTAAG
G
CTTAA
AATTC
G
EcoRI
Restriction enzymes cut DNA a specific sites.
e.g., EcoRI recognizes GAATCC.
GAATTC
CTTAAG
GAATTC
CTTAAG
G
CTTAA
AATTC
G
G
CTTAA
AATTC
G
EcoRI cut
Mix and ligate
G
CTTAA
AATTC
G
G
CTTAA
AATTC
G
Recombinant
molecules
GAATTC
CTTAAG
GAATTC
CTTAAG
Parental
molecules
Cut two DNAs with EcoRI, mix and ligate.
Voila, recombinant DNA!
Sealing of the broken
phosphodiester bond
is called ligation and
performed with an
enzyme called DNA
ligase.
Small protein (191 amino acids) expressed fromanterior lobe of pituitary
Essential for normal development
Promotes growth, especially in children
Growth Hormone (GH)
Mutations that eliminate the function GH1 generesult in severe dwarfism
Too much GH in childhood results in gigantismRobert Pershing Wadlow
Too much GH in adults resultsin acromegaly
GH
Activated GH receptor
Inactive GH receptor
Binding of GH to cell-surface receptor leads to
transcriptional regulation of specific genes.
Transcription factor
GH target gene
Injected growth hormone can be used to treat:
*growth hormone deficiency (GHD) in pediatric patients
*growth failure associated with chronic renal insufficiency(CRI) prior to kidney transplantation
*short stature associated with Turner syndrome
*growth hormone deficiency (GHD) in adults
In the 1960s and 70s, children were treated withgrowth hormone isolated from human cadavers.(80 cadavers for 1 year of treatment)
In 1985, the FDA banned this practice becauseseveral patients died from a fatal brain disorder
known as Creutzfeldt-Jacob Disease (CJD). CJDwas caused by contaminating prions in thegrowth hormone extract.
In 1985, Genentech introduced Protropin, arecombinant GH made in bacteria.
Some GH history How was human growth hormone(HGH) produced in bacteria?
Make DNA copy of hGH mRNA. This copy isknown as a complementary DNA or cDNA.
Clone cDNA into plasmid.
Introduce recombinant plasmid in bacteria (E.coli).
Induce expression of gene and purify HGH.
BALCO Chief on Sports Doping Scandal
Victor Conte Tells '20/20' He Created Illegal Drug Regimens for Top AthletesDec. 3, 2004 — Victor Conte, a man at the center of an anti-doping scandal that has rocked the toptiers of the sports world, tells "20/20" he tailored illegal drug regimens for top athletes, includingOlympic track stars Marion Jones, Kelli White and Tim Montgomery.
.
.Conte, founder of the California-based Bay Area Laboratory Co-Operative, which is facing federalcharges for distributing steroids and other illegal performance-enhancing drugs to athletes, sayshe supplied Jones with a variety of illegal drugs from August 2000 through September 2001. Heclaims to have supplied her with a substance called "the clear," EPO, human growth hormone, andinsulin.
Reduce Fat / Cellulite
Gain Strength
Improve Memory
Re-Hydrate Skin
Regulate Sleep
Heighten Mood
And Much More...
Bovine growth hormoneInjection of recombinant BGH increases milk production and
is often used in dairy farming.
Pros:
Increased milk production.
Reducing the number of dairy cows needed reduces the
production of methane, a greenhouse gas.
Cons:
Concern about health risks of having BGH and additional
proteins in milk.
Increased mastitis (udder infection) in cows.
Agribusiness uses BGH to compete with small dairy farmers,
who can!t afford the drug.
Transgenic mice and fish
The growth hormone gene has
been engineered to be expressed
at high levels in animals.
The result--BIG ANIMALS
The rat GH gene was cloned behind the metallothionein
promoter that is induced with heavy metals. The mouse
on the left has the transgene and was fed heavy metals.
Transgenic mice are 2-3 times larger than siblings thatlack the transgene.
Transgenic mice
Ocean pout antifreeze gene promoter-chinook salmon GH
transgene in atlantic salmon
One major concern:
Transgenic salmon will escape from fisheries and breedwith strains in the wild. If the transgenic fish have a
mating advantage and are less fit, they could have anegative effect on the normal population.
Potential solutions to this problem:
Raise sterile fish.
Raise the fish inland away from coastal waters and thusbreeding populations of salmon.