Cloned Mice: How They’re Made and Used in Science

A cloned mouse is a genetic duplicate of another, created through a laboratory technique rather than conventional reproduction. This process results in an organism with the same DNA as the original. The ability to produce genetically identical animals has made them a significant tool in scientific research, allowing for more precise studies of diseases and treatments by ensuring a uniform genetic background.

The Process of Cloning a Mouse

The creation of a cloned mouse is a multi-step process using a method called somatic cell nuclear transfer (SCNT). It begins with two mice: one that will be cloned and a separate egg cell donor. Scientists take a somatic cell, any cell from the body other than a sperm or egg cell, from the mouse they intend to clone. The nucleus of this cell contains the complete genetic blueprint of that animal.

Separately, an unfertilized egg cell is harvested from a donor mouse. The egg cell’s own nucleus is removed in a procedure known as enucleation, leaving it empty of its original genetic material. The nucleus from the somatic cell is then injected into this enucleated egg, which now contains the genetic material of the mouse to be cloned.

To initiate development, the reconstructed egg is treated with a chemical solution or an electrical pulse. This stimulation prompts the egg to begin dividing as if it had been fertilized, forming an early-stage embryo. This embryo is then surgically implanted into the uterus of a surrogate mother mouse. If successful, the surrogate gives birth to a mouse that is a genetic copy of the somatic cell donor.

This technique saw a breakthrough in 1998 with the creation of Cumulina, the first mouse cloned from an adult somatic cell. This achievement demonstrated that the DNA in a specialized adult cell could be reprogrammed to direct the development of a whole new individual.

Scientific Applications of Cloned Mice

The genetic uniformity of cloned mice is useful for creating animal models of human diseases. Scientists can take a somatic cell from a mouse with a specific genetic mutation and use it to generate a population of cloned mice. These mice will all carry the disease-causing gene, providing a consistent model to study disease progression and test potential therapies.

Cloned mice also play a part in pharmacology and toxicology. By administering a new drug to a group of genetically identical mice, researchers can get a clearer picture of its effects on the body and determine a safe dosage range. This reduces the chance that results are skewed by individual differences in metabolism.

Furthermore, cloned mice are used to investigate complex biological processes like aging. By creating clones from an aged animal, scientists can study how cellular and molecular changes associated with aging are passed on. This provides insights into the mechanisms that drive the aging process.

Health and Lifespan of Cloned Mice

Despite being genetic duplicates, cloned mice often exhibit health issues not seen in their naturally conceived counterparts. A common observation is a tendency toward obesity, with clones developing weight problems even under standard dietary conditions. This is often accompanied by metabolic complications.

Additionally, cloned mice have shown a higher incidence of tumor formation and compromised immune systems, which can lead to a shortened lifespan. The first cloned mouse, Cumulina, lived to an age of two years and seven months, a typical lifespan for her strain. However, many subsequent clones have not been as robust, experiencing premature death.

The underlying cause of these health issues is believed to be incomplete epigenetic reprogramming. While a clone’s DNA sequence is identical to the original, the epigenome is not always properly reset. The epigenome consists of chemical marks on DNA that act as on/off switches for genes. During SCNT, these patterns from the adult somatic cell nucleus must be erased and re-established to match those of a normal embryo.

When this reprogramming is incomplete, some genes may remain silent while others are improperly expressed. This faulty gene regulation can disrupt normal development and physiological functions, leading to the observed health problems and contributing to health disparities between clones and their donors.

Animal Welfare and Scientific Limitations

A major challenge in the cloning of mice is the low efficiency of the SCNT process. The procedure has a very high failure rate, and for every successful clone born, a large number of attempts are required. This involves numerous egg cells and multiple surrogate mothers.

This low success rate raises animal welfare considerations. The hormonal treatments used to stimulate egg production in donor females can be physically taxing. Surrogate mothers undergo surgical procedures for embryo implantation and may experience complications during pregnancy, including a high rate of miscarriages and stillbirths.

Many cloned embryos that implant fail to develop correctly, leading to developmental abnormalities or death before birth. Of the clones that are born live, a substantial percentage suffer from health problems from birth or die shortly after, highlighting existing technical hurdles.

These limitations mean producing cloned mice is a resource-intensive and ethically complex endeavor. The scientific community continues to research ways to improve the efficiency and safety of the SCNT technique. The goal is to refine the process to reduce the number of animals needed and improve health outcomes for the clones.