COMMON INBRED STRAINS

Among the many inbred strains, the great majority of biomedical research, including genomic research, is based on a relatively few mouse strains, including C57BL/6, BALB/c, C3H/He, 129, FVB, and outbred Swiss stocks.

The reader is referred to other sources for more comprehensive information regarding the myriad pos­sibilities of background pathology among laboratory mice (see Section “General References on Diseases of Mice”). This text is not intended to provide such depth of coverage, but herein provides a brief synopsis of important disease characteristics of the major strains/ stocks of mice. The specific lesions are described further in later sections of this chapter.

C57BL/6 (B6) mice are the gold standard “background strain” for GEMs created by homologous recombination. Many mutant alleles and transgenes are backcrossed onto this strain. There are a number of other related “black” strains, including C57BL/10 (B10). B6 mice were initially bred for their longevity. Their melanism is manifested by their coat color, as well as melanin pig­ment in heart valves, splenic capsule and trabeculae, meninges, cerebral vessels, Harderian glands, and para­thyroid glands. Common strain-related spontaneous diseases include hydrocephalus, hippocampal neurode­generation, microphthalmia and anophthalmia, age- related cochlear degeneration and hearing loss, and malocclusion.

BALB/c mice (BALB/c, BALB/cBy, et al.) are albinos. Mature males are rather pugilistic, requiring separate housing for particularly fractious individuals. Dys­trophic epicardial mineralization of the right ventricular free wall is common, and they are prone to development of myocardial degeneration and auricular thrombosis. Corneal opacities are commonly found, and they often develop conjunctivitis, blepharitis, and periorbital abscesses. Hypocallosity (corpus callosal aplasia) is fre­quent, and they develop age-related hearing loss. BALB mice are remarkably resistant to spontaneous amyloido­sis, in contrast to other mouse strains. The livers of normal BALB mice feature a moderate amount of hepa­tocellular fatty change. The most common tumors of BALB mice are pulmonary adenomas, lymphomas, Harderian gland tumors, and adrenal adenomas. Myo­epitheliomas of salivary, preputial, and other exocrine glands are also relatively common in this strain.

C3H∕He mice are agouti mice that are blind due to rd1 mutation (Pde6b^rd1) and are also prone to corneal opaci­ties and hearing loss later in life. They frequently develop focal myocardial and skeletal mineralization and myo­cardial degeneration. C3H/HeJ mice develop alopecia areata as they age. They are susceptible to exogenous murine mammary tumor virus (MMTV)-induced mam­mary tumors and develop a relatively high incidence of mammary neoplasia later in life due to endogenous MMTV.

129 mice rank high in the panoply of mousedom as the most frequent source of embryonic stem (ES) cells, from which most targeted mutant mice are derived. The 129 mouse is not a single strain, and in fact “129” is represented by 16 recognized strains and substrains. This is due to accidental and intentional genetic contamina­tion of the original 129 strain by various laboratories. Thus, the designation 129 is followed by P, S, T, or X, and other designations, in addition to substrain determi­nants. Genetic differences between the targeting con­struct and the ES cells can significantly influence efficiency of homologous recombination. The differences among 129 mice are not subtle, with variation in coat color, behavior, and other characteristics, including pat­terns of pathology. Hypocallosity is relatively common in many 129 mice. 129 mice, like B6 mice, are prone to pulmonary proteinosis and epithelial hyalinosis. Mega­esophagus occurs in some types of 129 mice. Blepharitis and conjunctivitis are common in 129P3 mice. 129/Sv mice are renown for development of testicular teratomas (aka embryonal carcinomas). Other common neoplasms in 129 mice are lung tumors, Harderian gland tumors, ovarian tumors, and hemangiosarcomas.

FVB/N mice are inbred Swiss mice that gained popu­larity for creation of transgenic mice in an inbred genetic background. They are blind due to homozygosity of rd1 allele (Pde6b^rd1) and prone to seizures. Many lines of FVB mice develop persistent mammary hyperplasia and hyperplasia or adenomas of prolactin-secreting cells in the anterior pituitary, but mammary tumors are rare (unless through transgenesis). Common neoplasms include tumors of lung, pituitary, Harderian gland, liver, lymphomas, and pheochromocytomas.

NOD mice are inbred Swiss mice that were selectively bred for cataracts, and during that process were found to develop type 1 diabetes (nonobese diabetes (NOD)).

Outbred Swiss mice are all closely related derivatives of a small gene pool of founder animals that were inbred for many generations in various laboratories before out­breeding, primarily by commercial vendors. Outbred Swiss mice are often erroneously considered “wild­type” for comparison with inbred mice. As noted previ­ously, they are far from outbred and differ genetically from inbred mice. Many, but not all, Swiss mouse stocks have retinal rdi degeneration (homozygous recessive), reflecting their high degree of homozygosity. Swiss mice are particularly prone to amyloidosis, which is a major life-limiting disease. They develop a variety of incidental lesions, and the most common tumors are lymphomas, pulmonary adenomas, liver tumors, pituitary adenomas, and hemangiomas/sarcomas, among others.