The beige (Bg<sup>J</sup>) mutation

History of the beige mutation

The name of this mouse mutation represents the color of affected mice in the original description of the beige (bg) mutation that arose at Oak Ridge National Laboratory, as a radiation-induced mutation (Kelley, 1957; Davisson and Lewis, 1990). These mice were on an agouti (A/-) black (B/-) background and exhibited decreased pigmentation of ear, tail and dorsal hair, resulting in the subterminal band being yellow, the middle dark gray, and the base very light gray. The mice had a cafe-au-lait or beige coloration (Witham and Lane, 1991).

A spontaneous remutation, the beige-J (bgJ), arose at The Jackson Laboratory in the C57BL/6J inbred strain. This strain is a non-agouti (a/a), black (B/B) mouse. The result is a dark (charcoal) gray colored affected mouse (Witham and Lane, 1991). This latter mouse, the beige-J, is the mutation commonly used by many scientists today. A second remutation, bg2J, has occurred at The Jackson Laboratory in the C3H/HeJ strain. Dihybrid crosses of congenic parental strains have been used to produce an albino-beige mouse (Robison and Kuwabara, 1978).

Gross lesions

The mutant mouse is easily distinguished from heterozygous or wild type controls. The hair is slightly lighter in coloration. Eye color varies from ruby to almost black. Reduced pigmentation is also evident on the ear and tail (Green, 1989). The shade of color may vary on different genetic backgrounds, depending on alleles at other coat color loci that may be carried by the strain. Other gross lesions represent background characteristics of the inbred strain that the mutation is fixed on (such as ophthalmic anomalies on the C57BL/6J background) or infectious diseases secondary to the immunosuppression features of the mutation.

Microscopic lesions

The decrease or dilution of the coloration of hair and other pigmented tissues is due to the reduced number, enlargement and clumping of melanin granules. In normal hair, the pigment granules are numerous and distributed uniformly along the length of the hair shaft. In the beige mouse, the melanosomes are reduced in number and clumped compared to littermate controls (Hearing, et al., 1973). All tissues containing cells with various types of cytoplasmic granules have giant lysosomes. These include granulocytes, lymphocytes, hepatic parenchyma, renal proximal tubules, central nervous system, exocrine and endocrine pancreas, ducts of various glands, thyroid follicles, type II pneumocytes and mast cells (Green, 1989; Oliver and Essner, 1973; 1975). Aging changes include a progressive neurological disorder accompanied by nearly complete loss of Purkinje cells in the cerebellum at a year and a half of age (Murphy and Roths, 1978).

Immunologic and biochemical lesions

A variety of immunological deficiencies or abnormalities associated with the granular defects are well known for the beige mutation. These include defective and reduced bactericidal activity of granulocytes (Gallin, et al., 1974), severe deficiency of natural killer (NK) cells (Roder, 1979), and a defective cytotoxic T-cell and antibody response to allogeneic tumor cells (Carlson, et al., 1984; Saxena, et al., 1982). A variety of lysosomal enzymes are decreased in neutrophils (Takeuchi, et al., 1986). Heterozygotes also have a platelet storage, pool deficiency and serotonin deficiency within the platelets, resulting in prolonged bleeding times (Holland, 1976; Novak, et al., 1981). This can be corrected by bone marrow grafts from normal mice (Novak, et al., 1985).

Background lesions

The inbred strain, C57BL/6J, has a number of known, but poorly documented, pathological anomalies that are often misdiagnosed as infectious diseases or complications of the mutation being studied. Skin lesions include alopecia that occurs around the time of weaning followed by regrowth of hair, adult-onset alopecia, papular dermatitis, and chronic ulcerative dermatitis as the mice age. A variety of ophthalmic anomalies occur that are associated with malformations of the lens in utero. Hydrocephalus occurs with low incidence.

Beige mice have been reported to have a decreased life span when compared to a control group of C57BL/6J mice. The mutants also have lower body weights than controls (Goodrick, 1977).

Because the beige mutation causes specific types of immunodeficiencies, it is not surprising that these mice are more susceptible to infectious diseases. This has been reported for a variety of spontaneous and experimental infections (Lane and Murphy, 1972; Shellam, et al., 1981; Shellam, et al., 1985).

Homologous human disease

Chediak-Higashi syndrome in human beings is essentially identical to the mutant phenotype of the beige mouse (Windhorst and Padgett, 1973; Blume and Wolff, 1972; Hoskin, et al., 1991). In fact, observations on the NK cell deficiency in beige mice led to investigations of human patients for this specific defect, which was then identified (Roder, et al., 1980; Haliotis, et al., 1980).

Homologous animal diseases

Diseases virtually identical to Chediak-Higashi disease of humans have been identified in a variety of domestic and wild animal species including Persian cats (Kramer, et al., 1977), Hereford cattle (Padgett, et al., 1964), Brangus cattle (Ayers, et al., 1988), Aleutian mink (Padgett, et al., 1964), foxes (Nes, et al., 1983; Fagerland, et al., 1987), and killer whales (Taylor and Farrell, 1973).

Common uses for the beige mutation

This mutation is a homologue of the rare human disease Chediak-Higashi syndrome. Methodical study of the mouse mutation has been utilized to identify similar abnormalities in human patients (Roder, et al., 1980; Haliotis, et al., 1980). The beige mutation, often in combination with other mutations such as pale ear (ep), has also been used to study the biology of pigment and pigment genes (Novak, et al., 1980; Novikoff, et al., 1979). The morphologic feature of giant lysosomes has been a useful marker for identifying and studying hematopoietic stem cells (Ash, et al., 1981). The most common use of this mutation, however, is a biomedical tool, utilizing the various immune system abnormalities to study induction and metastatic spread of cancer (Salomon, et al., 1980; Talmadge, et al., 1980; Haliotis, et al., 1985; Carlson, et al., 1984), immunomodulation of infectious diseases (Solomon, et al., 1985; Morahan, et al., 1982; Shellam, et al., 1981; Shellam, et al., 1985), hypersensitivity (Galli and Hammel, 1984); and bone marrow grafts (Harrison and Carlson, 1983; Murphy et al., 1973).

Availability of mice

The beige mutation (alleles bgJ or bg2J) is available as a single mutation on the C57BL/6J or C3H/HeJ inbred strain backgrounds from The Jackson Laboratory. The original bg allele is available in a double mutant with the satin (sa) mutation (McGarry, et al., 1984) on the SB/Le inbred strain. Additional double mutants, including beige and nude (nu) and others may be available occasionally from the research colonies developed and maintained by immunologists on The Jackson Laboratory staff.


Ash P, Loutit JF, Townsend KMS. Osteoclasts derive from hematopoietic stem cells according to marker, giant lysosomes of beige mice. Clin Orthop 155:249-258, 1981.

Ayers JR, Leipold HW, Padgett GA. Lesions in Brangus cattle with Chediak-Higashi syndrome. Vet Pathol 25:432-436, 1988.

Blume RS, Wolff SM. The Chediak-Higashi syndrome: studies of four patients and a review of the literature. Medicine 51:247-280, 1972.

Carlson GA, Marshall ST, Truesdale AT. Adaptive immune defects and delayed rejection of allogeneic tumor cells in beige mice. Cell Immunol 87:348-356, 1984.

Davisson MT, Lewis SE. Chromosome aberrations associated with induced mutations: effect on mapping new mutations. Branbury Report 34: Biology of Mammalian Germ Cell Mutagenesis. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp 195-206, 1990.

Galli SJ, Hammel I. Unequivocal delayed hypersensitivity in mast cell-deficient and beige mice. Science 226:710-713, 1984.

Gallin JI, Bujak JS, Patten E, Wolff SM. Granulocyte function in the Chediak-Higashi syndrome of mice. Blood 43:201-206, 1974.

Green MC. Catalog of mutant genes and polymorphic loci. In: Genetic Variants and Strains of the Laboratory Mouse. Lyon MF, Searle AG (eds.), Oxford Univ Press, Oxford, pp 12-403, 1989.

Goodrick CL. Body weight change over the life span and longevity for C57BL/6J mice and mutations which differ in maximal body weight. Gerontology 23:405-413, 1977.

Fagerland JA, Hagermoser WA, Ireland WP. Ultrastructure and stereology of leukocytes and platelets of normal foxes and a fox with a Chediak-Higashi-like syndrome. Vet Pathol 24:164-169, 1987.

Haliotis T, Ball JK, Dexter D, Roder JC. Spontaneous and induced primary oncogenesis in natural killer (NK)-cell-deficient beige mutant mice. Int J Cancer 35:505-513, 1985.

Haliotis T, Roder JC, Klein M, Ortaldo J, Fauci AS, Herberman RB. Chediak-Higashi gene in humans. I. Impairment of natural-killer function. J Exp Med 151:1039-1048, 1980.

Harrison DE, Carlson GA. Effects of the beige mutation and irradiation on natural resistance to marrow grafts. J Immunol 130:484-489, 1983.

Hearring VJ, Phillips P, Luztner MA. The fine structure of melanogenesis in coat color mutants of the mouse. J Ultrastruct Res 43:88-106, 1973.

Holland JM. Serotonin deficiency and prolonged bleeding in beige mice. Proc Soc Exp Biol Med 151:32-39, 1976.

Hoskin DW, Anderson SK, Stankova J, Haliotis T, Roder JC. Immunologic and nonimmunologic consequences of the beige mutation. In: Immunologic Disorders in Mice. Rihova B and Vetvicka V (eds.), CRC Press, Boca Raton, FL, pp 251-263, 1991.

Kelley EM. Mouse News Lett 16:36, 1957.

Kramer JW, Davis WC, Prieur DJ. The Chediak-Higashi syndrome of cats. Lab Invest 36:554-562, 1977.

Lane PW, Murphy ED. Susceptibility to spontaneous pneumonitis in an inbred strain of beige and satin mice. Genetics 72:451-460, 1972.

McGarry RC, Walker R, Roder JC. The cooperative effect of the satin and beige mutations in the suppression of NK and CTL activities in mice. Immunogenetics 20:527-534, 1984.

Morahan PS, Coleman PH, Morse SS, Volkman A. Resistance to infections in mice with defects in the activities of mononuclear phagocytes and natural killer cells: effects of immunomodulators in beige and 89Sr-treated mice. Inf Immun 37:1079-1085, 1982.

Murphy ED, Harrison DE, Roths JB. Giant granules in beige mice. A quantitative marker for granulocytes in bone marrow transplantation. Transplantation 15:526-530, 1973.

Murphy ED, Roths JB. Purkinje cell degeneration, a late effect of beige mutations in mice. Jackson Lab Ann Rep 49:108-109, 1978.

Nes N, Lium B, Braend M, Sjaastad O: A Chediak-Higashi-like syndrome in Arctic blue foxes. Finsk Veterinaertidsskrift 89:313, 1983.

Novak EK, Hui S-W, Swank RT. Platelet storage pool deficiency in mouse pigment mutations associated with several distinct genetic loci. Blood 63:536-544, 1984.

Novak EK, McGarry MP, Swank RT. Correction of symptoms of platelet storage pool deficiency in animal models for Chediak-Higashi syndrome and Hermansky-Pudlak syndrome. Blood 66:1196-1201, 1985.

Novak EK, Swank RT, Meisler MH. Pigmentation and lysosome function in mice homozygous for both pale ear and beige-J pigment genes. Genet Res Camb 35:195-204, 1980.

Novikoff AB, Leuenberger PM, Novikoff PM, Quintana N. Retinal pigment epithelium. Interrelations of endoplasmic reticulum and melanolysosomes in the black mouse and its beige mutant. Lab Invest 40:155-165, 1985.

Oliver C, Essner E. Distribution of anomalous lysosomes in the beige mouse. A homologue of Chediak-Higashi syndrome. J Histochem Cytochem 21:218-228, 1973.

Oliver C, Essner E. Formation of anomalous lysosomes in monocytes, neutrophils, and eosinophils from bone marrow of mice with Chediak-Higashi syndrome. Lab Invest 32:17-27, 1975.

Padgett GA, Leader RW, Gorham JR, O'Mary CC. The familial occurrence of the Chediak-Higashi syndrome in mink and cattle. Genetics 49:505-512, 1964.

Robison WG, Kuwabara T. A new, albino-beige mouse: giant granules in retinal pigment epithelium. Invest Ophthalmol Vis Sci 17:365-370, 1978.

Roder JC. The beige mutation in the mouse. I. A stem cell predetermined impairment in natural killer cell function. J Immunol 123:2168-2173, 1979.

Roder JC, Haliotis T, Klein M, Korec S, Jett JR, Ortaldo J, Heberman RB, Katz P, Fauci AS. A new immunodeficiency disorder in humans involving NK cells. Nature 284:553-555, 1980.

Salomon J-C, Creau-Goldberg N, Lynch NR. Cancer induction by methylcholanthrene and metastatic spread of transplantable tumor in Chediak-Higashi (beige) mice. Cancer Immunol Immunother 8:67-70, 1980.

Saxena RK, Saxena QB, Adler WH. Defective T-cell response in beige mutant mice. Nature 295:240-241, 1982.

Shellam GR, Allan JE, Papadimitriou JM, Bancroft GJ. Increased susceptibility to cytomegalovirus infection in beige mutant mice. Proc Natl Acad Sci, USA 78:5104-5108, 1981.

Shellam GR, Flexman JP, Farrell HE, Papadimitriou JM. The genetic background modulates the effect of the beige gene on susceptibility to cytomegalovirus infection in mice. Scand J Immunol 22:147-155, 1985.

Solomon JB, Forbes MG, Solomon GRA. A possible role for natural killer cells in providing protection against Plasmodium berghei in early stages of infection. Immunol Lett 9:349-352, 1985.

Takeuchi K, Wood M, Swank RT. Lysosomal elastase and cathepsin G in beige mice. Neutrophils of beige (Chediak-Higashi) mice selectively lack lysosomal elastase and cathepsin G. J Exp Med 163:665-677, 1986.

Talmadge JE, Meyers KM, Prieur DJ, Starkey JR. Role of natural killer cells in tumor growth and metastasis: C57BL/6J normal and beige mice. J Natl Cancer Inst 65:929-935, 1980.

Taylor RF, Farrell RK. Light and electron microscopy of peripheral blood neutrophils in a killer whale affected with Chediak-Higashi syndrome. Fed Proc 32:822abs, 1973.

Windhorst, DB, Padgett G. The Chediak-Higashi syndrome and the homologous trait in animals. J Invest Dermatol 60:529-537, 1973.

Witham B, Lane PW. Why C57BL/6J-bgJ mice are not beige. JAX Notes 445:4, 1991.