Gene editing creates buff beagles

A pair of buff beagles may have the edge in doggy body-building contests. Scientists in China changed the dogs’ genes to make the small hounds extra-muscular.

The dogs are the latest addition to a menagerie of animals — including pigs and monkeys — whose genes have been “edited” by scientists. The pups’ genes were altered with a powerful technology called CRISPR/Cas9.

Cas9 is an enzyme that cuts through DNA. CRISPRs are small pieces of RNA, a chemical cousin of DNA. The RNAs guide the Cas9 scissors to a specific spot on DNA.  The enzyme then snips the DNA at that spot. Wherever Cas9 cuts the DNA, its host cell will try to repair the breach. It will either paste the cut ends together or copy unbroken DNA from another gene and then splice in this replacement piece.

Tying together broken ends can result in mistakes that disable a gene. But in the dog study, those so-called mistakes were actually what the Chinese scientists had been aiming for.

Liangxue Lai works at the South China Institute for Stem Cell Biology and Regenerative Medicine in Guangzhou. His team decided to test whether CRISPR/Cas9 would work  in dogs. These researchers used it to target the gene that makes myostatin. This myostatin protein normally keeps an animal’s muscles from getting too big. Breaking the gene can cause muscles to bulk up. Natural mistakes in the gene, called mutations, work that way in Belgian Blue cattle and dogs called bully whippets. These mutations have not caused those animals health problems.

The researchers injected the new gene-editing system into 35 beagle embryos. Of 27 puppies born, two had edited myostatin genes. The team reported its success October 12 in the Journal of Molecular Cell Biology.

Most cells in an animal have two sets of chromosomes and, thus, two sets of genes. One set comes from mom. The other is inherited from dad. These chromosomes provide all of an individual’s DNA. Sometimes the copy of a gene from each chromosome set match one another. Other times they do not.

One of the two dogs that had mutations in the myostatin gene was a female puppy named Tiangou. She was named after a “heaven dog” that appears in Chinese myth.  Both copies of the myostatin gene in all of her cells contained the edit. At 4 months, Tiangou had more muscular thighs than an unedited sister.

The second puppy carrying the new edit was male. He carries double mutations in most of his cells, but not all. He was named Hercules, after an ancient Roman hero noted for his strength. Alas, Hercules the beagle was not more muscular than other 4-month-old puppies. But both Hercules and Tiangou have packed on more muscle as they’ve grown. Lai says their fur may now be concealing how ripped they are.

That the researchers could produce two puppies with edited myostatin genes shows that the gene scissors works in dogs. But the small share of puppies with the gene edit also shows that the technique is not very efficient in these animals. Lai says the process just needs to be improved.

Next, Lai and his colleagues hope to make mutations in beagles that mimic natural genetic changes that play a role in Parkinson’s disease and in human hearing loss. That might help scientists who study those diseases develop new therapies.

It also might be possible to use the gene scissors to create dogs with specific features. But Lai says the researchers have no plans to make designer pets. 

Power Words

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Cas9      An enzyme that geneticists are now using to help edit genes. It can cut through DNA, allowing it to fix broken genes, splice in new ones or disable certain genes. Cas9 is shepherded to the place it is supposed to make cuts by CRISPRs, a type of genetic guides. The Cas9 enzyme came from bacteria. When viruses invade a bacterium, this enzyme can chop up the germ’s DNA, making it harmless.

cell  The smallest structural and functional unit of an organism. Typically too small to see with the naked eye, it consists of watery fluid surrounded by a membrane or wall. Animals are made of anywhere from thousands to trillions of cells, depending on their size.

chromosome  A single threadlike piece of coiled DNA found in a cell’s nucleus. A chromosome is generally X-shaped in animals and plants. Some segments of DNA in a chromosome are genes. Other segments of DNA in a chromosome are landing pads for proteins. The function of other segments of DNA in chromosomes is still not fully understood by scientists.

CRISPR     An abbreviation — pronounced crisper — for the term “clustered regularly interspaced short palindromic repeats.” These are pieces of RNA, an information-carrying molecule. They are copied from the genetic material of viruses that infect bacteria. When a bacterium encounters a virus that it was previously exposed to, it produces an RNA copy of the CRISPR that contains that virus’ genetic information. The RNA then guides an enzyme, called Cas9, to cut up the virus and make it harmless. Scientists are now building their own versions of CRISPR RNAs. These lab-made RNAs guide the enzyme to cut specific genes in other organisms. Scientists use them, like a genetic scissors, to edit — or alter — specific genes so that they can then study how the gene works, repair damage to broken genes, insert new genes or disable harmful ones.

DNA (short for deoxyribonucleic acid) A long, double-stranded and spiral-shaped molecule inside most living cells that carries genetic instructions. In all living things, from plants and animals to microbes, these instructions tell cells which molecules to make.

embryo  The early stages of a developing vertebrate, or animal with a backbone, consisting only one or a or a few cells. As an adjective, the term would be embryonic — and could be used to refer to the early stages or life of a system or technology.

enzymes  Molecules made by living things to speed up chemical reactions.

gene  (adj. genetic) A segment of DNA that codes, or holds instructions, for producing a protein. Offspring inherit genes from their parents. Genes influence how an organism looks and behaves.

gene editing    The deliberate introduction of changes to genes by researchers.

genetic   Having to do with chromosomes, DNA and the genes contained within DNA. The field of science dealing with these biological instructions is known as genetics. People who work in this field are geneticists.

molecular biology  The branch of biology that deals with the structure and function of molecules essential to life. Scientists who work in this field are called molecular biologists.

mutation  Some change that occurs to a gene in an organism’s DNA. Some mutations occur naturally. Others can be triggered by outside factors, such as pollution, radiation, medicines or something in the diet. A gene with this change is referred to as a mutant.

myostatin     A protein that helps control the growth and development of tissues throughout the body, mostly in muscle. It’s normal role is to ensure that muscles don’t become overly large. Myostatin is also the name given to the gene that contains the instructions for a cell to make myostatin. The myostatin gene is abbreviated MSTN.

RNA  A molecule that helps “read” the genetic information contained in DNA. A cell’s molecular machinery reads DNA to create RNA, and then reads RNA to create proteins.

technology   The application of scientific knowledge for practical purposes, especially in industry — or the devices, processes and systems that result from those efforts.