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As a hobby breeder, breeding rats to involves a combination of breeding methods. Starting with high quality rats and using inbreeding, line breeding and occasional outcrosses will help a breeder to reach the goal of improvement in the line.
Bettering the breed should encompass several factors: health, temperament, and conformation. The three methods used to selectively breed towards this goal are inbreeding, line breeding, and outcrossing.
Tracking the offspring and future generations of any line (or outcross) provides essential data.

Definition of a Line

A line is defined in the Merriam-Webster dictionary as:
1: Family, lineage
2: a strain produced and maintained especially by selective breeding.

A line does not happen over night, it can take years and involves multiple inbred and line bred generations.
The persistent breeding of unrelated animals does not designate a line.

It seems a common practice in some parts of the fancy to outcross repeatedly (generation after generation) without testing for health issues, and without stopping to evaluate the rats, without attempting to set desirable traits, etc. This practice does not meet the definition of having a line(s) and should not be referred to as such.

Outcrossing can be used to strengthen or add a trait to a line, but it is the inbreeding of those offspring back to the foundation line that helps it to remain true to the original definition of a line.
Animals outcrossed whose offspring are bred to the outcrossed animals would become a related or sub line, but would denote a new line or “branch.”

Line Breeding

Line breeding is a term that breeders use to denote a family of inbred rats that begins with a single or pair of foundation rats. Rat’s within a line will have the same (or closely) lineage.

Lineage is defined by Merriam-Webster as:
1 a: descent in a line from a common progenitor
2: a group of individuals tracing descent from a common ancestor ; especially : such a group of persons whose common ancestor is regarded as its founder

Line breeding is accomplished by tightly inbreeding as well as by breeding rats that are less closely related (aunt/nephew, uncle/niece, cousin/cousin, grandparents/grandchildren).
Linebreeding is used to set certain traits as well as to eliminate negative ones, therefore it is important not to breed two animals together that have the same fault.
One must also not breed related rats together just because of the pedigree, not all the rats from each litter are the same genetically.
Considering health traits, temperament, and physical features will enable a breeder to choose the correct rats for each other, not just because they are related or because of sentimental attachment.

Inbreeding

Inbreeding is defined by Merriam-Webster as:
1: the interbreeding of closely related individuals especially to preserve and fix desirable characters of and to eliminate unfavorable characters from a stock

Inbreeding is used extensively in the breeding of many species and can be used either to set a positive trait or identify a potentially negative trait depending upon the choices made.
When two unknown rats, or even rats from different known lines, are brought together for a breeding the offspring may all appear to be robust and free of any unwanted genetic issues.

Test breeding the siblings and/or breeding an offspring back to the parent can help to identify undesirable traits by doubling up on the reccesives of the two different parents.

It is said, by some, that test breeding can create offspring with genetic issues. This is true at times, and yet it is important that this be done so that the health and viability of the new line can be evaluated and possibly discontinued if there are problems.
Without multiple close test breeding negative recessive traits are swept under the rug and may be perpetuated indefinitely only to resurface later in a much larger gene pool.

Inbreeding Tolerance

Different species have different degrees of inbreeding tolerance. And there are situations, such as when dealing with endangered species, where close inbreeding can be disastrous.
In some mammal populations a high inbreeding coefficient can lead to inbreeding depression. And, it is not always about the accumulation of bad traits. It is possible for the natural percentage of certain lethal genes that each organism carries with no adverse effects to accumulate and cause problems such as immune deficiencies and fertility issues.

With rats, the safe inbreeding quotient is quite high. In laboratories a line is not even considered inbreed until the 20th generation. Inbred lab strains are often achieved by breeding brother to sister in each generation. It is important, in research, to use healthy animals that are as genetically similar as possible so that test results show consistent data.

Outcrossing

The Merriam-Webster dictionary defines outcross as:
noun:
1: a cross between relatively unrelated individuals 2: the progeny of an outcross
transitive verb:
1: to cross with a relatively unrelated individual or strain

Outcrossing is done to introduce new traits that are missing from a line. Dominate genes, such as rex, will exhibit in the first generation.
Recessive genes such as dumbo ear or a color dilution will typically show in the second generation if the offspring from the outcross (who now carry but do not exhibit the trait) are breed back to the parent used as an outcross (who exhibits the trait and is therefore homozygous for the trait) or if the siblings are bred together.

Type & Outcrossing

Altering color
The coat color of a rat can be altered by breeding it to a rat of a different color and then back breeding to the outcrossed parent.
Breeding to a rat with an eye dilution can also change the color in a line. On the other hand, strengthening a color can be achieved by breeding to rats carrying less dilutions.
Modifying Physical Structure
Outcrossing can be a used as a tool to improve eyes or ears (shape, placement, or size). It can also be used in hopes of improving the size, shape, and/or length of the body, the head, or the tail.
Adding or Modifying Patterns or Markings
Breeding to marked or patterned rats can enable you to add or improve the trait in your line.
Temperament and Outcrossing
Little is known on how well temperament can be improved by outcrossing. And it can sometimes be difficult to determine if temperament issues are environmental or genetic. Generally the safest action is to avoid breeding any animal with a poor temperament, particularly if the rat shows aggression.
Health Issues & Outcrossing
Outcrossing can be used to improve vigor in a line that has been inbred or linebred for many generations if the litters appear to become consistently smaller or the pups no longer have the strong health (vigor) or size that is normally seen in that line.
It can also be done in an effort to “breed out” a particular medical trait, such as a tendency toward tumors, diabetes, or in a line exhibiting a genetic defect such as megacolon. Considering that a great many of these issues are rooted in genetics, breeding an outcross does not always eliminate a problem. It can mask it and perpetuate the issue.
Outcrossing may eliminate a health issue over time if the correct animals are chosen for breeding: the ones that somehow did not get the recessive(s) as well as outcrossed rats that also aren’t carrying the problematic gene.
All too often, outcrossing to get rid of a problem just hides the recessives enabling the negative trait to show up later in the line (and in other lines as the rats are outcrossed more).
A good example of well meaning, but not necessarily well thought out, “avoidance” outcrossing involves the breeding of hairless lines that have lactation issues. Breeding to haired females who carry hairless will ensure that the offspring between them and the hairless sire will be fed. Unfortunately, there is a good chance that many of the offspring will still carry the genes that contribute to lack of lactation.
Some issues are connected to certain traits, as is the case in “high white rats” who are associated with aganglionic megacolon. Breeding away from the trait can only be accomplished by breeding away from the markings.

Hobby Breeder Considerations- Outcrossing

When doing an outcross, think very carefully about which animal to bring in, consider the reason why you are choosing to bring this particular rat in and if the rat will complement the rats you are working with.
You want to improve those few traits with the outcross, but you do not want to ruin the work you have already done. With each positive trait the new rat also will be bringing in every problem and weakness from its own line and adding it to yours.

Hints

Know the history of the outcross (health, temperament, and genetic)

Have a goal in mind when choosing an outcross.

Breed only to a few rats from your existing line(s).

Test breed after an outcross for negative issues by inbreeding siblings or back breeding to parents

Track the offspring placed with other breeders or owners

Let the offspring mature as long as possible before breeding to give yourself more time to evaluate health and temperament

Wait to breed the outcrossed rats back into your original line particularly if the outcross has a little known or unknown history.

Considering the potential that each outcross could bring in many problems over the next several generations that it may not be worth it to take the chance ruining your years of work.
It is wise to maintain a portion of the line separate from outcrosses to ensure the perpetuation of the healthy line in the event an outcross has negative results. You do not want to bring in something that is going to give you a whole new problem to “breed out.”

Strain

A strain is a variation of a particular species that possesses minor differences in its characteristics (physiological or chemical) though still remain distinguishable.

A strain requires homozygosity through close inbreeding methods such as brother/sister mating or by back crossing offspring with parents.
Homozygosity is the presence of the same alleles at one or more loci, it is “genetic sameness.”

The word strain comes from the Middle English word streen: meaning progeny, lineage, as well as from the Old English streon: meaning gain, acquisition.

Merriam-Webster dictionary defines strain as:
1 b: a group of presumed common ancestry with clear-cut physiological but usually not morphological (structural) distinctions
2 a: inherited or inherent character, quality, or disposition

Strains in the laboratory can include: inbred, outcrossed, and sub strains. In the lab it takes 20 generations of inbreeding to produce a strain that will be 95% genetically similar. With 40 inbred generations the percentage reaches 99.5%

Origin and Use

Origin
Rats were first used in Europe for nutritional studies as early as 1850. As time passed rats were kept in labs and used for other testing.

The specific inbreeding of rats was primarily achieved in America. The oldest known strains of inbred rats were started by Helen Dean King in 1909 at the Wistar institute in Pennsylvannia. She had two lines of albino rats, one of which became known as the King Albino (Later named the PA strain).
By 1920 she had reached the 135th generation of inbreeding the PA line.
King also started an inbred strain from wild Norway rats that she caught locally. When it reached generation 35 it was designated the BN (Brown Norway) strain.

Another scientist at Wistar, Margaret Dean Lewis, was the initiator of the LEW (Lewis) strain which reached its 8th generation in 1956.

These strains were the origination either in part/or in whole of many of the modern day rat strains. The direct descendants of the Wistar strains are still in use today.

Use
The fact that the rat’s physiology as well as its short life span have made it the lab animal most responsible for advances in medicine. Having such closely related strains in the laboratory is important to providing consistent data to researchers. It provide lines of rats with no apparent health or disease issues as well as rats with specific genetic issues.

The rats with no apparent genetic issues help the researchers more about such things as pathogenic disease, neurological injuries, toxicology, behavior, and pharmacology.

Rats with specific genetic issues are used by comparative medicine researchers to learn more about disease process and genetic disorders, behavior, treatment of diseases, causes of disorders, and pharmacology.

Comparative medicine research involving rats, although hard for rat lovers to sometimes deal with, has enabled medical doctors to learn more about the treatment and prevention of many things that people suffer from such as cancer, diabetes, birth defects, and many others.

References

The Laboratory Rat, Second Edition 2006 Edited by Mark A. Suckow, Steven H. Weisbroth, and Craig L. Franklin

Posted on March 26, 2006, 13:15, Last updated on May 5, 2006, 17:40 | Breeding