Research with Animals

Scientists Unexpectedly Create Epilepsy in Rats   August 2002 - Cosmiverse

Mice eggs matured in the test tube  August 2002 - BBC 

Pufferfish DNA Yields Clues To Human Biology  August 2002 - Science Daily 

Dogs Can Learn  August 2002 - BBC

Ratbot - Scientists Pilot Rats With Electrodes   Reuters - May 2002
   Controlling the movements of rats to help find victims
   of disasters such as earthquakes - to hunt bombs, etc.

A Monkey Moves Cursor by Thinking - Wash. Post - March 2002

Color-change mouse created

The mouse can change from albino to brown and back

June 19, 2001 - BBC - Journal Genes and Development

Scientists in the United States have created a genetically modified mouse that changes color.

The pure white rodent grows a brown coat when a special supplement is added to its diet.

By studying the function of particular genes during development we can begin to understand how an alteration in the function might lead to human disease.

When the sugary substance is withdrawn, the mouse reverts to its white coat.

Researchers say the work could lead to a better understanding of human genetic diseases and cancer.

The study is bound to prove controversial among groups opposed to animal research.

Dr Heidi Scrable of the University of Virginia, Charlottesville, said: "It demonstrates that we can turn genes on and off in the mouse, which is the principal experimental animal that we have for modelling human diseases."

She said the mouse would be an important tool for medical research since some genes are virtually identical in the mouse and the human.

One particular challenge is cancer. The team plans to study a gene implicated in many cancers in a bid to find out how common tumours develop.

Dr Scrable told BBC News Online, "By studying the function of particular genes during development we can begin to understand how an alteration in that function might lead to human disease."

Pink eyes, brown eyes

The team used genetic engineering and natural breeding to alter the genes of an albino strain of mouse.

The rodents lack pigment in the eyes, skin, and fur because of a genetic mutation so they have pink eyes and a pure white coat.

The neuroscientists added two extra genes to the mice - one of them a normal mammalian pigment-producing gene.

The other gene, derived from a bacterium, is a regulator that switches the pigment gene on and off in response to a dietary trigger.

The scientists ended up with mice that can change their coat colour and even the colour of their eyes.

Adding a sugar-like substance to an animal's drinking water switches on the gene that makes the pigment melanin.

The mouse then grows a brown coat and its pink eyes become dark. On removing the sugar, the albino coat grows back, but the animal's eyes stay black because the pigment does not break down.

Ocelot Is Born From Frozen Embryo -Ohio Zoo

August 24, 2000 - Reuters

Cincinnati Zoo officials said on Wednesday an ocelot had been reproduced by frozen embryo transfer in a world first for the species, a procedure aimed at preserving various subspecies of the endangered cat.

Bill Swanson, head of the zoo's Center for Research of Endangered Wildlife, said the kitten was born as a result of implanting three frozen embryos in an adult female.

One of the embryos was born last week after 83 days of gestation. Announcement of the birth was delayed until the zoo could make sure the kitten would survive.

While the process has been used with other animals it had not been successful, until now, with an ocelot, zoo officials said.

The baby ocelot was named Sihil, a Mayan word meaning ``to be born again.'' Its gender will not be checked for several weeks to allow an extended period of bonding with its mother, one of six ocelots at the zoo.

While there are about 120 ocelots living in captivity in North American zoos, most are mixtures of various subspecies and not representative of any single wild population.

Swanson said researchers plan to reestablish populations of the subspecies by using frozen embryos from wild animals and implanting them in the mixed-breed zoo cats, starting with a Brazilian subspecies. The offspring will be purebred subspecies.

Ocelots are somewhat similar in appearance to leopards but smaller in size. They inhabit densely wooded areas in Texas and Latin America.

Prized by hunters for their spotted coats, they have been on the U.S. endangered species list since 1972 and are considered endangered throughout their range.

Crocodile heart valve found to regulate oxygen in blood

August 23, 2000 - Nando

An unusual heart valve in crocodiles that puzzled scientists for nearly 200 years has finally been explained and may be central to crocs' ability to stay underwater for hours.

The valve recirculates oxygen-poor blood back into the bloodstream, apparently to sustain the animal's most vital organs, researchers said.

The Swedish and Australian team studied a common saltwater crocodile, focusing on a valve in its right ventricle called a cogged-teeth valve. It resembles interlocked human knuckles.

By injecting the reptile with a heart-slowing drug, they prompted the notched valve to close off an entry to the artery leading to the lungs. It acted like a shunt, diverting oxygen-poor blood away from the lungs and back into the bloodstream.

The experiment was done in the laboratory. The researchers suspect that wild crocodiles regulate blood flow in a much more complex manner by opening and closing the valve when they submerge for long durations.

"We believe they're using this valve to ration their oxygen when they're underwater," said Michael Axelsson, an associate professor of zoophysiology at the University of Goteborg in Sweden.

The research appears in Thursday's issue of the journal Nature.

The cogged-teeth valve is composed of nodules of connective tissue unlike the thin, leaf-like valves typically found in vertebrate hearts. It was first described by scientists in the early 19th century, but its function remained unclear.

All crocodiles are believed to have the heart valve, though Axelsson and an Australian colleague looked only at the Crocodylus porosus, a man-eater found along the coasts of Australia and Papua New Guinea.

Kent Vliet, an alligator biologist at the University of Florida in Gainesville, Fla., said the laboratory work clearly reveals the blood-flow pattern within the croc's complex heart.

"Now what we really need to know is whether or not these structures are actually used by the animals in nature. Do freely diving crocodiles really shunt blood away from their lungs and into the bloodstream?" Vliet said.

Axelsson said his team is working with an American engineer to develop an implantable heart monitor that can be inserted in wild crocodiles.

Calls to crack chimp genome

Chimps are 99 percent genetically identical to humans

August 24, 2000 - BBC

US scientists are calling for an international effort to decode the genome of the chimpanzee.

They believe the project could explain why humans, and not chimps, succumb to diseases like Aids and malaria.

But some researchers are sceptical about the plans.

They fear much of the genetic data would be meaningless or confusing.

The drive to sequence the genome of great apes is being spearheaded by Ajit Varki, Professor of Medicine at the University of California, San Diego.

"The chimpanzee and the bonobo share nearly 99 percent of human genomic sequences," he told the journal Genome Research.

"Knowing the complete genome of at least one of these species will give us a window into genes that contribute to 'human-ness'."

Fighting Aids

The main imperative for a primate genome project is to find out why humans develop certain diseases that other primates are immune to.

Chimps are immune to the HIV virus

Learning about the genetic differences between chimps and humans could help in the search for new treatments for human diseases as diverse as Aids, Alzheimer's, malaria and cancer.

Diseases that kill humans in large numbers usually have little impact on the lives of great apes.

Most strikingly, chimps infected with the HIV virus do not get Aids. And, despite sharing a gene that predisposes humans to getting Alzheimer's disease, chimps do not develop the condition.

Professor Morris Goodman of Wayne State University, USA, is one of the supporters of the project.

"There's a big effort now to persuade the groups that are concerned with large-scale genome sequencing that they should undertake a primate genome project," he told BBC News Online.

Genetic cousins

Knowing the genetic make-up of the chimp might shed light on human characteristics such as our big brains and complex social behaviour.

And a primate genome project could also aid conservation efforts, by raising public awareness of the close genetic relationship between humans and other primates.

But Professor Grahame Bulfield, director of the Roslin Institute, Scotland, famous for cloning Dolly the sheep, questioned the value of sequencing the genome of primates.

"The mere fact that there are only one or two percent genetic differences between chimps and human beings still means that they are going to differ in many thousands of DNA sequences," he told BBC News Online.

"Working out which ones are responsible for the differences between chimps and humans and, of those, which are important in the diseases that differ between chimps and humans is a very difficult problem."

Meanwhile, scientists in Japan have already begun decoding the genomes of great apes in a separate venture.

The initiative, known as Project Silver, aims to compare gene expression in chimps and humans.

Skinny mice defy obesity

Lean mouse: Hope for the clinically obese

July 27, 2000 - BBC

Genetically engineered mice which never put on weight could hold the key to a fat- free future for humans, say scientists.

Researchers at Smith Kline Beecham and Cambridge University, UK, have developed mice that eat far more than normal but remain leaner and lighter.

The lab rodents over-produce a human protein which ensures food is turned into heat, rather than stored as fat.

Reporting in the journal Nature, Dr John Clapham and colleagues say their mice make large amounts of Uncoupling Protein 3 (UCP-3) in the mitochondria of their muscle cells.

Mitochondria are often described as the tiny internal combustion engines of cells. They unlock the energy contained in food to make a chemical fuel called adenosine triphosphate (ATP).

But extra UCP-3 causes the mice to burn off energy without making ATP - their bodies produce more heat instead. This process makes the metabolic rate of the transgenic mice step up a gear. As a result, they are able to eat large amounts of food yet weigh less than normal mice.

"If you slip the clutch on the car, you are still using up fuel, but no matter how hard you rev the engine that car isn't going to move and all that fuel is expended as heat".

Dr Clapham and his team write in their journal paper that even though the transgenic mice ate 15-54% more food than normal mice, their fat-tissue mass was 44-57% less.

The success of the work gives scientists hope that they will be able to develop a similar therapy for humans.

"What these mice have told us, in fact, is that this is a viable drug target to treat obesity," Dr Clapham said. However, he stressed that diet and exercise should remain the first courses of action.

New generation of drugs

He said any new therapy should be used to aid the degree of weight loss achieved on a diet, and crucially help the maintenance of that loss over time.

The mice eat as much as they like but stay thin.

And he said new drugs would work differently to the current generation of appetite suppressers.

"If you over-eat or under exercise you will put on weight. Appetite suppressers, of course, reduce appetite but new drugs based on our research would act on the other side of that equation.

"They would increase energy expenditure and they would increase metabolic rate, which could be very important."

Professor Nick Finer, director of the Centre for Obesity Research, Luton and Dunstable Hospital in Luton, UK, welcomed the new study.

"We know from food surveys and large studies that part of the problem with obesity is our low level of energy expenditure and activity.

"This research shows us is it is possible to treat obesity by increasing energy expenditure, in this case in mice but it might also be possible in people as well."

Scientists Induce Self Repair in Mouse Brain

June 22, 2000 - Nature

Scientists have managed to make new neurons grow in an area of the brain once thought to lack the ability to regenerate, raising hopes of developing new ways of treating neurological diseases and head injuries.

The researchers induced the creation of the neurons in the neocortex of lab mice by triggering stem cells, or precursor cells, that already exist in the brain.

Other research has shown that under specific conditions, transplanted stem cells can form new neurons. The new study indicates that transplantation may not be needed.

Instead, a combination of molecular signals can accomplish the same thing, said Dr. Jeffrey Macklis, a neuroscience professor at Harvard Medical School and Children's Hospital who led the study. It was published in Thursday's issue of the journal Nature.

The researchers were encouraged to find that the new cells showed evidence that they were incorporated into the brain circuitry. The cells migrated to areas populated by the dead neurons and sprouted axons, or connections, into the proper tissue.

Macklis and fellow researchers Sanjay Magavi and Blair Leavitt triggered the new growth by killing specific neurons - a procedure that the scientists do not envision as part of any future treatments.

Future experiments will focus on understanding exactly what triggers the creations of neurons and developing drugs or molecular manipulations that do not involve killing cells to create new ones, Macklis said.

Any new treatments for neurological disorders like Alzheimer's and Parkinson's disease or nervous system injuries are many years and experiments away.

"We just have to keep in mind that you can do things in the brain of a mouse that you can't necessarily do in people," said Bruce Dobkin, director of the neurologic rehabilitation and research program at the University of California at Los Angeles.

And the fact that a connection sprouted does not mean it functions like the neuron it replaced.

Platypus And Oppossum Studies Reveal Ancient Origin Of Genetic Battle Of The Sexes

April 22, 2000 - Science Daily

By comparing genes in the opossum and the platypus, Duke University Medical Center researchers have uncovered evidence that questions the origin of "genomic imprinting" -- a process by which a gene's expression is governed solely by which parent donated the gene copy, rather than by the classic laws of Mendelian genetics, in which genes are either dominant or recessive.

The findings also resolve questions surrounding the structure of the mammalian evolutionary tree and may open the door to better evaluation of carcinogenic agents.

The theory of the evolution of genomic imprinting holds that imprinted genes, which usually are related to growth and development, represent a genetic "battle of the sexes" -- a competition between paternally imprinted genes that lead to enhanced fetal growth and maternally imprinted genes that restrict growth, saving nutrients for the mother herself.

According to this theory, animals without a lengthy fetal development stage -- such as marsupials, whose infants leave the womb while still embryonic and develop in external pouches, and egg-laying monotremes, the most primitive order of mammals -- were not expected to be imprinted.

However, in the April 21 issue of the journal Molecular Cell, a research team led by graduate student Keith Killian and principal investigator Randy Jirtle reports that a particular gene, called M6P/IGF2R, is imprinted in the marsupial opossum but not in the platypus, a monotreme.

Until now, imprinted genes had not been examined in such primitive mammals.

"This finding suggests that M6P/IGF2R imprinting evolved a lot farther back than we thought, in a precursor animal between what are currently the monotremes and marsupials," Jirtle said.

He is a professor of radiation oncology and associate professor of pathology at Duke University Medical Center and a member of the Duke Comprehensive Cancer Center.

The M6P/IGF2R gene codes for the receptor for another molecule, called "insulin-like growth factor 2" (IGF2), whose gene is also imprinted in many mammals.

Both genes are involved in growth, but imprinted M6P/IGF2R is maternally expressed, while IGF2 is paternally expressed.

The researchers' finding that M6P/IGF2R is imprinted in the opossum, but not in the platypus, supports the idea that imprinting is due to a "battle of the sexes," but the primary requirement seems to be competition for survival among the young, rather than a lengthy fetal development period.

"Young opossum must crawl to reach the pouch and latch on, and this is consistent with a battle of the sexes for nutrient allocation as a reason for imprinted genes," said Jirtle. "For the opossum, it's literally a race for life.

But since opossum have only a 13-day gestation period, a lengthy fetal development stage is not necessary for imprinting to arise."

Unlike puppies or piglets, once newborn opossum latch on to the mother's nipple, they can't let go until they grow large enough to open their mouths.

Since there are only a dozen nipples for up to 50 babies in a single litter, competition is important. The faster a baby opossum can climb, the more likely it is to survive, and the more likely its genes will be passed on.

On the other hand, there's no active competition on the part of young platypus.

While competition to ensure genes' survival can explain why imprinting first evolved for marsupials, it doesn't answer why imprinted genes still exist in higher mammals, such as humans.

In lower mammals a single group of offspring can be fathered by more than one male, but in higher mammals that is very unlikely, making competition between offspring to keep their fathers' genes in the pool unnecessary.

"About 30 imprinted genes are known, but there may be as many as 500. We don't know if humans need these imprinted genes, or if we would be OK without them," Jirtle said.

"Nevertheless, we have them and as a result of their limited expression, they become targets for developmental diseases and cancer."

If something happens to the functional copy of an imprinted gene, there's no back-up as with other genes. "These are growth promoting and growth inhibiting genes, for the most part," Jirtle explained. "If the balance is altered, you could lose a tumor suppressing gene or turn on an oncogenic one."

In fact, mutations of IGF2 and M6P/IGF2R appear to be early steps in a wide variety of cancers, scientists say.

In many tumors, both copies of growth-inducing IGF2 are turned on, despite the gene being imprinted in humans.

For M6P/IGF2R, which is not imprinted in humans, both copies normally function. However, in more than 60 percent of human liver cancers, 30 percent of breast cancers and 50 percent of lung cancers at least one copy of this growth-suppressing gene doesn't work.

Since humans have two functioning M6P/IGF2R genes, but mice have only one due to imprinting, it's reasonable to think that humans should be more resistant to cancer-causing agents. Right now, however, possible carcinogens are tested on mice.

Jirtle and Killian want to develop a "better" mouse -- one with two working copies of M6P/IGF2R that might better reflect human susceptibility to cancer-causing agents.

Another of the study's findings should help them figure out how to turn on the mouse's silent M6P/IGF2R gene. While other researchers have reported finding the region of DNA that controls the imprinting of M6P/IGF2R in mice, this entire region was missing in the opossum.

Since Killian has no doubt that the gene they cloned in the opossum is in fact the homologue of M6P/IGF2R, the current finding likely means that the actual controlling region has yet to be found. "The proposed controlling element is not there in the opossum," Jirtle explained.

"Either the opossum has a completely different, unique, and as-yet-unidentified mechanism to control imprinting of this gene, or the proposed region in the mouse is not the actual controlling region."

If they can find the region in the opossum that turns the imprinted genes on and off, and if they can then locate that region in the mouse, the researchers could potentially develop a strain of mice that can't imprint the M6P/IGF2R gene. If so, they'll have found their better mouse.

The scientists' studies of imprinting also have important implications for understanding the mammalian evolutionary tree, Jirtle said. The presence of imprinted genes in the opossum but not platypus suggests that marsupials are more closely related to eutherians -- the name for mammals whose offspring develop in the womb -- than they are to monotremes.

This relationship supports the proposed version of the mammalian evolutionary tree in which monotremes branched off the main evolutionary trunk before marsupials; rather than another version that places marsupials and monotremes as two twigs on a single branch.

In order for the second proposed evolutionary tree to be correct, given the current finding, imprinting would have had to evolve twice -- once on the marsupial twig and again on the eutherian branch -- in a process called convergent evolution.

That's very unlikely, say the scientists.

Birds are composers, creating music that rivals the best human musicians, according to ornithologist Luis Baptista

February 24, 2000 - AP

At the annual meeting of the American Association for the Advancement of Science in Washington, D.C., Baptista compared bird songs to the music of several famous composers, including Bach and Beethoven.

He's found a bird in the Chiapas rainforest near Guatemala, the white-breasted wood wren, which sings the opening bars of Beethoven's 5th symphony.

Baptista says it's simply coincidence that the songs are the same.

The similarity may come from similar brain structure, says Baptista. The part of our brains that produces music may be wired like birds, or vice versa.

Besides looking at the connections between composers and their feathered friends, Baptista also investigates bird languages. He believes that chicks learn their songs from older birds, like babies learn language.

"I'm looking at how birds learn their language and pass it down by oral tradition," he says.

When blackbirds are raised in a soundproof box, they sing nonsense compared to the songs of blackbirds raised in a group, says Baptista. This also happens in children raised without exposure to language.

Additional evidence for language learning comes from German blackbirds, says Baptista, citing evidence from a previous study. The blackbirds sing a tune that inspired a violin piece by Beethoven, he says. Since they're still sweetly singing the same song after 180 years, it must have been taught to each new generation.

He also studied a woodpecker that could drum in seven different pitches, memorizing certain spots on a log that produced different sounds. The woodpeckers, and many other birds, use their calls to attract potential mates, says Baptista.

Ulrike Griebel, a biologist at the Lorenz Institute in Vienna, agrees. "I think it conveys an evolutionary advantage," she says. Birds who make beautiful music get the girls.

Only certain types of birds, like blackbirds, dickey birds, and hummingbirds, learn their songs like a language, says Baptista. Others inherit their knowledge.

Blackbirds can also transpose songs into different keys, a feat few humans can do without instruction. "Birds have two vocal cords, and can sing two songs at the say time," says Baptista.

Baptista plans to look for more examples of feathered musicians in the future, hoping to find a bridge between art and science.