The Mongolian gerbil (Meriones unguiculatus) is extensively used as an animal model in studies of pharmacology [1] , parasitology [2] , aging [3] , oncology [4] , and reproduction [5] [6] . Gerbils used in scientific research originated from 20 pairs captured in the basin of the Amur River in eastern Mongolia and were imported into Japan in 1935. They were sent to the Kitasato Institute for rickettsial studies [7] . Agouti gerbils in our laboratory have been kept as a closed colony since 1983 from their origins at Tokyo Women’s University and Tokyo University of Agriculture [6] . By repeated sub-mating of these gerbils, we have created the inbred agouti strain MON/Num/a (Figure 1(A)). In addition, albino gerbils were introduced from Chiba City Zoo, and their phenotype has been maintained in the heterozygous state by sub-mating with MON/Num/a gerbils. After repeated sub-mating, we established a closed colony of MON/Num/c albino gerbils (Figure 1(B)).

In general, albinism is an autosomal recessive disorder, which occurs as a consequence of mutations in genes involved in regulating melanin biosynthesis [8] [9] . Many albino mouse strains (e.g., A, AKR, BALB/c, and ICR) lack pigmentation owing to mutations in the Tyrosinase (Tyr) gene [10] . Tyrosinase encoded by Tyr is well known as the key enzyme in pigment biosynthesis in mammals and is the first enzyme in the melanin synthesis pathway, converting tyrosine to dihydroxyphenylalanine (DOPA) and then to dopaquinone [11] [12] . Albinism caused by mutations in Tyr has been characterized in human [13] , mouse [10] [14] [15] , rat [16] , rabbit [17] , cat [18] , ferret [19] , and cattle [20] . The first report of complete albinism (cc) in gerbil was published by Matsuzaki et al. [21] . Additionally, some coat-color phenotypes (e.g., black chinchilla medium, aac^chmc^chm; siamese, aac^chmc^h; dark-tailed white, aac^hc^h; recessive yellow, ee; black recessive yellow, aaee; and fading recessive yellow, e^fe^f), considered to be related to Tyr mutations, have been reported [22] [23] . However, genetic evidence of albino mutation in gerbil has not been characterized yet.

Here, to identify the gene responsible for albinism in gerbil, we analyzed the cDNA sequence of the Tyr gene in albino phenotype gerbil (MON/Num/c) and compared it with that of wild-type gerbils (agouti, MON/Num/a; and MON/Jms/GbsSlc).

Albinism in gerbil was first reported by Matsuzaki et al. [21] , but not since, and genetic evidence of albino mutations has not been characterized yet. Oculocutaneous albinism (OCA), which is a group of autosomal recessive diseases in humans and other animals, is characterized by reduced or absent melanin in skin, hair, and eyes. Type 1 OCA (OCA1) results from mutations in the Tyr gene, which codes for tyrosinase, a copper- containing enzyme that catalyzes the first two steps in the melanin biosynthesis pathway: the hydroxylation of tyrosine to DOPA and the subsequent oxidation of DOPA to dopaquinone [26] . It is well known that OCA1 is caused by nonsense, missense, frameshift, or splice-site alterations in Tyr. Various mutations causing OCA1 have been reported. In human, a single-base C-to-A substitution in exon 3, which causes a

T373K alteration, is frequently found [27] . In BALB/c mouse, a G-to-C mutation at position 387, which causes a C85S alteration, is common [14] [15] . In albino rat, a single G-to-A mutation at position 896 in exon 2 causes an R299H alteration [16] . In the cattle, a frame-shift mutation caused by an insertion in codon 316 is associated with complete albinism [20] . The absence of codon 325 in the domestic albino cat causes a premature stop codon [18] . In the white New Zealand rabbit, complete albinism is due to a missense alteration at residue 373 [17] . As these reports show, most albino mutations in mammals result from a missense or frameshift mutation in Tyr. In albino gerbil, on the other hand, we find two missense mutations (R77H encoded in exon 1 and Q473R encoded in exon 5) in tyrosinase (Figure 4), which are conserved all albino gerbils we tested. Therefore, we suggest that both missense mutations of Tyr are conserved in the albino phenotype and are responsible for albinism in gerbil. The gerbil is commonly used as a model animal in studies of a wide range of infectious diseases by reason of its high sensitivity to various parasite [2] and pathogens [1] . However, the mechanism of these sensitivities remains to be identified. So far, we have reported molecular information on immunoglobulin [28] [29] and variation in the IgG subclass [30] in the agouti (MON/Num/a) strain to investigate acquired immunity in gerbil, and have established methods for producing gerbil mAb [31] and cytokines [32] with heterohybridoma techniques. Although immune systems have not been compared in detail between albino (MON/Num/c) and agouti strains yet, use of the albino strain for immunological research may further contribute to the establishment of new strains as models of infectious disease.

In this study, we identified two missense mutations in exons 1 and 5 of the Tyr gene in albino gerbil. These mutations support the functional significance of tyrosinase in albinism in gerbil. However, we did not determine the full Tyr cDNA sequence in gerbil. As a next step, phenotypic characterization of albino-by-agouti crosses is needed to clarify how these missense mutations result in albinism. Our results will provide valuable information on albinism in gerbil and will contribute to the establishment of albino strains.

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Ukaji, T., Iwasa, M.A. and Kai, O. (2016) Tyrosinase (Tyr) Gene Mutation in Albino Mongolian Gerbil (Meriones unguiculatus). Open Journal of Animal Sciences, 6, 259-268. http://dx.doi.org/10.4236/ojas.2016.64031