Those Inbred Lab Mice

Inbred lab mice are so healthy you only have to keep them in a sterile bubble and wear biohazard getup just to watch them.

The Pure Blood Brigade™ (licensed for use from Jess Ruffner) will sometimes invoke laboratory mice as the go-to example of a perfectly healthy inbred population. Here’s a quote from NSDTR-apologist and accomplice to Dr. Claire Wade, Dr. Danika Bannasch:

I don’t know if you are familiar with inbred mice.  There are 100s of laboratory strains that are completely inbred- ie homozygous at every locus.  They breed prolifically and are healthy.  They are not living in the wild but neither are domestic dogs.

To verify the health of laboratory mice I went to Jackson Laboratory–the “most important supplier of lab animals to science“–and viewed their “Breeding Strategies for Maintaining Colonies of Laboratory Mice.”  The manual claims that the breeding strategies that are used to create inbred lab mice are:

“safe, reliable, economical, efficient, and ensure that the mouse strains produced are genetically well-defined.”

Notice that they don’t claim that the mouse strains produce healthy mice that live long and have good temperaments, they are just genetically well-defined (highly homozygous).  Here are snippets which hint at the deep underlying dysfunction that is found in inbred lab mice:

• Reproductive life span. Typically, laboratory mice can breed for about seven to eight months, producing four or more litters (Table 1). However, some strains produce only one or two litters, usually because strain-specific characteristics or mutant phenotype affect their fertility. AKR/J mice (000648) develop leukemia, and breeders must generally be replaced when they are about six months old. C3H/HeJ mice may stop breeding early because they have a high frequency of ovarian cysts and tumors. NOD/ShiLtJ (001976) females may develop diabetes when they are 12 weeks old, but their reproductive lives can be extended with foot pad injections of Freund’s Adjuvant.

• Fertility. Fertility of inbred strains varies. For example, whereas nearly all breeding pairs of C3HeB/FeJ (000658) mice are fertile, less than half of C57L/J (000668) breeder pairs are fertile.

Wild mice breed for up to 24 months. Laboratory mice can breed for only 7-8 months.

Wild mice can have 5-10 litters per year, so 10-20 litters over their two year reproductive lifespan. These lab mice have 1-6 litters, the most popular strains average 3-4 litters.

Average wild mouse litter size is 10-12 pups. The mean litter size of the top 12 most popular lab strains are: 5.4, 5.2, 4.5, 5.0, 5.6, 4.0, 4.7, 7.3, 7.7, 5.8, 6.4, 4.9; so about 5 pups.

Birth defects in the pups. C57BL/6J (000664) mice tend to have more pups with hydrocephaly than do other strains. A/J (000646) mice tend to have relatively more pups with cleft palates, the incidence of which can be influenced by the uterine environment.

Hybrid vigor. Hybrid mice tend to have more, larger, and healthier litters than inbred strains.

Strain-specific behaviors. The aggressive behaviors of some strains and the poor mothering instincts of others affect breeding performance and pup survival. For example, SJL/J (000686) males are aggressive and attack their mates and offspring; NZB/BlNJ (000684) females are poor mothers.

Here we have pretty much the death knell for using lab mice as an excuse to inbreed dogs.  Aggressive behaviors and poor mothering are deal breakers for almost any decent dog breeder.  Birth defects in many breeds are at epidemic levels, and yet many breeders are so jaded they consider it normal. We should not consider it normal and those of us in healthy breeds should steel our spines against becoming such moral sellouts.

Oh, and hybrid vigor is real. We can reverse this.

Don’t let outcross breeders tell you otherwise, small litter sizes are actually a bonus! Who needs those extra offspring, they are just a hassle.

• Mutations and transgene effects. Some mutations are embryonic lethal; some cause infertility or reduced fertility; some affect mammary gland function. For example the Tg(SOD1*G93A)1Gur transgene (also found in several strains) induces neurodegeneration. The severity of such effects depends on strain background.

If you’ve been reading this blog for any amount of time you should be well aware of the embryonic lethal mutations that are prevalent in certain breeds of dog.  Many of these have been identified because they associate with a marked phenotype change of interest such as merle or bobtail. How many more exist that do not have a visible phenotype?

• Feed. Some strains of mice have bad teeth, no teeth, or other phenotypes that affect their ability to eat grain pellets. These mice need special foods, such as ground or dampened grain.

Does this remind you of the poor dentition we see in several toy breeds and especially hairless dogs?

Females of some strains are poor mothers (e.g., NZB/BlNJ, 000684) or cannot nurse, and a few mutations, such as toxic milk (Atp7btx) and lethal milk (Slc30a4lm), render the mother’s milk harmful to her pups.

I wonder if those toxic and lethal milk mothers were intentionally bred to have harmful milk or if those are just known side effects of strains used for other kids of research.

Some strains are so screwed up they are only viable by transplanting the ovaries of the inbred mice into healthier females:

Some strains are best maintained by ovarian transplantation. Homozygous B6C3Fe a/a-Csf1op/J (000231) females fail to lactate, and homozygotes of both genders are extremely fragile. Therefore, we transplant ovaries from a homozygous (op/op) female into a recipient female of a histocompatible strain. To quickly expand the colony, the donor ovaries may be quartered and each quarter ovary transplanted into a ovariectomized recipient female. We also maintain B6.V-Lepob/J mice (000632) by ovarian transplantation because, though the females produce functional gametes, they cannot sustain a productive pregnancy. Additionally, we maintain colonies of B6CBA-Tg(HDexon1)62Gpb/1J (002810), B6CBA-Tg(HDexon1)62Gpb/2J (004601), and B6CBA-Tg(HDexon1)62Gpb/3J,(006494) by ovarian transplantation to extend the breeding lifespans of the females. Although these females produce viable oocytes for a long time, they develop a progressive neurological disease that renders them physically incapable of mating or sustaining a pregnancy.

Fantastically healthy, no?

Don’t worry, not all inbred lab mice are satanic albino demons, some are really cute! And that makes everything ok.

But all is not lost, the manual provides some advice on how to maintain an outbred colony to turn to if your inbred strain crashes and burns.

Maintaining Outbred Stocks

The genomic diversity of individual outbred mice contrasts directly with the genetic identity among individual mice of an inbred strain. To maintain genetic diversity in an outbred colony, matings between related individuals should be avoided; however, some inbreeding may be inevitable over time in any relatively small, closed outbred colony.

Therefore, the following should be considered when establishing an outbred colony:

• Use numerous, genetically diverse founder mice

• Use a defined breeding scheme that is designed to minimize inbreeding: Several different outbred breeding program have been described (see Berry & Linder, 2007)

• While random breeding — using a random number table or computer program to select breeders — can be used, random breeding will result in occasional matings between closely related individuals

• Keep the colony at a minimum size of approximately 25 breeder males per generation

So if you’re interested in breeding dogs that burn out young, are riddled with disease, have nasty temperament issues, have trouble conceiving, develop horrible diseases young, etc., then believe that you too can develop an inbred strain and it’ll all turn out just dandy, just like those inbred lab mice.  Just be sure to buy yourself a nice dog bubble and some bio-hazard gear to wear around your dog while you keep it in a perfectly sterile environment after burying a truck load of its siblings and ancestors who died in the process of making your inbred little mess.

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About Christopher

Christopher Landauer is a fifth generation Colorado native and second generation Border Collie enthusiast. Border Collies have been the Landauer family dogs since the 1960s and Christopher got his first one as a toddler. He began his own modest breeding program with the purchase of Dublin and Celeste in 2006 and currently shares his home with their children Mercury and Gemma as well. His interest in genetics began in AP Chemistry and AP Biology and was honed at Stanford University.