Deer Mice As Laboratory Animals

Abstract

At the University of South Carolina, Columbia, South Carolina, Charlotte P. Joyner is Supervisor of Animal Care for the PGSC; Lisa C. Myrick, B.S., is Research Assistant; Janet P. Crossland is Stock Center Colony Manager and Staff Assistant for the PGSC; and Wallace D. Dawson, Ph.D., is Director of the Peromyscus Stock Center and Professor in the Department of Biological Sciences. At the University of South Carolina, Columbia, South Carolina, Charlotte P. Joyner is Supervisor of Animal Care for the PGSC; Lisa C. Myrick, B.S., is Research Assistant; Janet P. Crossland is Stock Center Colony Manager and Staff Assistant for the PGSC; and Wallace D. Dawson, Ph.D., is Director of the Peromyscus Stock Center and Professor in the Department of Biological Sciences. At the University of South Carolina, Columbia, South Carolina, Charlotte P. Joyner is Supervisor of Animal Care for the PGSC; Lisa C. Myrick, B.S., is Research Assistant; Janet P. Crossland is Stock Center Colony Manager and Staff Assistant for the PGSC; and Wallace D. Dawson, Ph.D., is Director of the Peromyscus Stock Center and Professor in the Department of Biological Sciences. At the University of South Carolina, Columbia, South Carolina, Charlotte P. Joyner is Supervisor of Animal Care for the PGSC; Lisa C. Myrick, B.S., is Research Assistant; Janet P. Crossland is Stock Center Colony Manager and Staff Assistant for the PGSC; and Wallace D. Dawson, Ph.D., is Director of the Peromyscus Stock Center and Professor in the Department of Biological Sciences. The laboratory mouse ( Mus domesticus ) and rat ( Rattus norvegicus ) remain the most widely used species of research rodents. Nevertheless, other rodent species (albeit in smaller numbers) are also consistently employed in laboratory research and teaching ( Jackson 1997 ). One species used increasingly in toxicological and epidemiological research, as well as in ecological, behavioral, and genetic studies, is the deer mouse ( Peromyscus maniculatus ) ( Figure 1 ) ( Barry 1975 ). Laboratory-bred wild-type deer mouse ( Peromyscus maniculatus ) of the bairdii Washtenaw (BW) stock. Wild deer mice are among the most abundant small mammals in North America. They range from Alaska to central Mexico, from Newfoundland to Virginia, and from Atlantic to Pacific oceans ( Hall 1981 ). Deer mice are absent only in the southeasternmost states, where they are replaced by related species. More than 60 formally described subspecies of deer mice occupy a wide variety of forest, prairie, and desert habitats from sea level to elevations of 14,000 ft or more. In nature, deer mice nest in logs and stumps or in shallow burrows beneath rocks and clumps of vegetation. They subsist on seeds supplemented with occasional crickets or other insects. Owls, snakes, foxes, weasels, and other small carnivores find these rodents a staple food source, and thus they play an important role in natural ecosystems ( King 1968 ; Kirkland and Layne 1989 ). Deer mice were first bred in captivity about 1916 by Francis Sumner at the Scripps Institution at La Jolla, California ( Sumner 1917 ). For the next half-century, a handful of investigators continued to collect and establish breeding stocks of these animals, which were used primarily to study genetic structure of small mammal populations. A particularly noteworthy large colony was maintained from about 1925 until 1975 by Lee R. Dice and his proteges at the University of Michigan. Several existing lines of deer mice trace to this Michigan colony. It was also during this time that many of the distinctive coat color mutants were originally isolated ( Rasmussen 1968 ). In 1962, the deer mouse colony at the University of South Carolina was established. Over the next 3 decades, more than 30 distinct “wild-type” and mutant genetic stocks were acquired, forming the nucleus of the Peromyscus Genetic Stock Center (PGSC 1 ). The PGSC, formally initiated in 1985, is supported in part by the National Science Foundation as a biological resource. At the time of this writing, approximately 3000 animals are maintained. The function of the PGSC is to provide the scientific community with genetically defined animals and to improve the deer mouse as a model for biological research. The deer mouse has distinct advantages for certain kinds of studies. Many of the advantages stem from the fact that this native species can be used as a laboratory standard for contrasting wild counterparts. For example, deer mice can be utilized to monitor environmental pollution using exposed wild animals compared with laboratory-bred controls ( Kucera 1988 ). A representative study is that of Schauber and others (1997 ), in which effects of insecticide ingestion were assayed in deer mice. Because deer mice are native, laboratory observations can be extrapolated to natural populations for ecological investigations. The existence of numerous deer mouse races and more than 50 closely related Peromyscus species, all in North America, also make the deer mouse a favorite subject for fine scale systematics studies in this country. Because many genetic variants in deer mice occur at loci homologous with those in the laboratory house mouse and rat, they are useful in parallel studies with more conventional laboratory species. Deer mice are appealing, alert creatures with large eyes and ears. The wild-type animal is sharply bicolored with a rich brown-gray above and white below. Handled properly by experienced persons, even with bare hands, the majority bite only rarely. Additionally, they are slightly smaller than most laboratory mice, and odor is negligible. Another major advantage is the ample genetic polymorphism in natural Peromyscus populations and various laboratory stocks that can be screened for specific variants of interest. For example, an outbred stock of deer mice was the source of the alcohol dehydrogenase “null” variant extensively employed in ethanol metabolism research ( Alderman and others 1987 ; Bradford and others 1991 ; Felder 1975 ). Two major disadvantages of deer mice as laboratory animals are the unavailability of highly inbred, genetically homogeneous strains and difficulty in handling due to their quickness and jumping ability. Both of these problems are being approached through controlled breeding. Because outbred stocks retain significant genetic polymorphism, they are not preferred when consistency of response is required, such as in dosage studies. However, as noted above, this same polymorphism provides a rich source of biochemical and molecular variation that can be tapped for genetic analysis. Development of highly inbred strains of Peromyscus has met with limited success. Although a number of lines of both deer mice and white-footed mice ( Peromyscus leucopus ) have been inbred by sib-sib and/or parent-offspring mating for more than 20 generations, inbred animals tend to have reduced fertility and viability. Selection for greater docility in deer mice has proved effective in the double recessive brown and silver coat color stock. A related species maintained in the PGSC, Peromyscus aztecus from Mexico, is easily handled and stands in marked contrast to Peromyscus melanophrys , also from southern Mexico. Peromyscus melanophrys is among the more aggressive species. Many aspects of the biology of the deer mouse and other Peromyscus species have been amply explored. Two general reference volumes, Biology of Peromyscus ( King 1968 ) and Advances in the Study of Peromyscus ( Kirkland and Layne 1989 ), are devoted exclusively to rodents of this genus. Literally thousands of laboratory and field studies have been conducted. Thus, these are laboratory animals whose natural ecology is very well documented. Particularly the physiology, reproduction, genetics, and behavior of deer mice have been extensively investigated (see citations in the 2 volumes referenced above). Buttler (1988 ) compiled a Peromyscus literature data base with more than 6000 citations, including 1380 titles between 1980 and 1987. A semiannual PEROMYSCUS NEWSLETTER is published by the PGSC and distributed to more than 600 individuals active in research with these rodents. This newsletter includes informal research accounts, summary information on genetics of deermice, recent literature citations, and other information of interest to subscribers. At the time of this writing, the Internet-accessible data bank Pero Base is under development. When completed, this data base will contain a large body of detailed information concerning all aspects of Peromyscus biology. The most active research areas utilizing deer mice and related species are ecology and epidemiology ( Table 1 ). Peromyscus have been implicated in 2 human diseases of current interest: (1) Deer mice ( P. maniculatus ) are carriers of the pathogen producing the recent hantaviral pulmonary syndrome (Four Corners disease) outbreak in the southwestern United States. (2) The deer mouse and the congeneric white-footed mouse are known hosts for the larval stage of the tick ( Ixodes ), which transmits the Lyme disease spirochaet ( Borrelia ) ( Burgess and Patrican 1987 ; Ubico and others 1996 ). These species are extensively employed in laboratory studies of the conditions described. Peromyscus are also used in aging research, since they are often long lived compared with house mice ( Mus ) ( Sacher and Hart 1978 ; Smith and others 1990 ). Research with Peromyscus based on 284 articles in the 1993 to 1997 scientific literature Does not include molecular systematics or population genetics. Includes molecular systematics. However, less than 25% of research activity with deer mice and their allies is for strictly “biomedical” research, in which more traditional laboratory animals are usually preferred. Deer mice and other Peromyscus have long been considered ideal for evolutionary research at the morphological ( Blair 1950 ; Dice 1940 ; Sumner 1932 ), biochemical ( Zimmerman and others 1978 ), cytogenetic ( Allard and Honeycutt 1991 ; Stangl and Baker 1984 ), and molecular levels ( Cassavant and others 1996 ; Kass and others 1992 ; Lansman and others 1983 ). Deer mice are a frequent species of choice for studies of biological rhythms ( Demas and others 1997 ; Nelson and Blom 1994 ), torpor ( Hulihan-Giblin and others 1993 ; Nestler and others 1996 ), and neurochemistry ( Hunt and Hooper 1993 ; Kavaliers and Innes 1993 ). The genus Peromyscus comprises approximately 55 existing and several extinct species of mouse-like rodents of the family Muridae (sensu lato), subfamily Sigmodontineae. Representatives of the genus first appear in the fossil record during the late Pliocene about 4 million years ago (MYA 1 ) and represent the North American phylogenetic branch of sigmodontine rodents that also includes wood rats, grasshopper mice, and American harvest mice ( Hibbard 1968 ; Hooper and Musser 1964 ). The evolutionary lines leading respectively to Peromyscus and murine rodents ( Rattus, Mus ) diverged from a common ancestral stock 17 to 30 MYA, probably in Asia, and deer mouse progenitors invaded North America from Siberia perhaps 20 MYA ( Catzeflis and others 1993 ; Sarich 1985 ). The systematics of Peromyscus is well studied, but some aspects remain controversial ( Carleton 1989 ; Hooper 1968 ; Osgood 1909 ; Stangl and Baker 1984 ). The genus traditionally is divided into subgenera and species groups ( Hall 1981 ). Different species vary greatly in size: The largest, Peromyscus thomasi and Peromyscus pirrensis , weighing 100 g or more, and the smallest, as little as 14 g as adults. However, of the numerous forms, only a few are widespread. P. maniculatus (deer mice) and P. leucopus (white-footed mice) are the most familiar and biologically best known species. Mature deer mice weight ranges from 16 to 35 g, depending on the subspecies. The tail is shorter than the head-body length in the prairie and desert races, but longer in the forest forms.Adult animals of the most frequently used laboratory stock ( P. m. bairdii ) typically weigh 18 to 21 g, with 85- to 90-mm head-body length and a tail length of 50 to 55 mm. Deer mice have distinctly bicolored tails. White-footed mice, also used extensively in research, are similar in size and other features to the deer mouse. The white-footed mouse is the most common wild Peromyscus species in the eastern United States. In some wild populations, white-footed mice are difficult to distinguish readily from deer mice, but they usually have a less distinct tail stripe and a narrower eye set. Nevertheless, these are distinct species and cannot be hybridized ( Dice 1933 ; Maddock and Dawson 1974 ). Mature white-footed mice maintained at the PGSC average 25 to 28 g in weight, 90 to 95 mm in head-body length, and approximately 70 mm in tail length. The reproductive biology of the 2 species in the laboratory is similar, except that the birth interval in white-footed mice averages about 2 days longer than the 27 days typical of deer mice. The California mouse ( Peromyscus californicus ), another species maintained at the PGSC, is larger than either the deer mouse or white-footed mouse. California mice are noteworthy because of their monagamous mating behavior and paternal participation in nurturing young ( Gubernick and others 1993 ; Ribble 1991 ). This species has received considerable attention from behavioral biologists. Approximately 50 loci representing coat color and morphological, behavioral, and biochemical variants have been described in the deer mouse from formal genetic crosses. Approximately 24 additional presumptive enzyme loci are known from variation in wild populations. A based on data groups and ( Dawson and 1993 ). The population and evolutionary genetics of variation are particularly well ( and others ; and 1989 ; ; 1978 ; Zimmerman and others 1975 ; among The deer all Peromyscus , has a number of ( and 1968 ). In contrast to murine has been in Peromyscus At 3 have been in deer mouse ( and others 1978 ), and is considerable variation in the species ( and others ; Stangl and Baker 1984 ). The has been ( and others 1994 ), but only 2 of the groups have been to and for P. maniculatus , P. and P. californicus and have been for several and example, and others 1994 ; Kass and others 1997 ; and others 1987 ; and others 1993 ). Many enzyme and variants are known for of deer mice ( and 1987 , 1989 ; Lansman and others 1983 ; and others ). Peromyscus molecular for several and have been hybridized in to Peromyscus ( Baker and 1990 ; and others ; and others ). Several Peromyscus molecular and are through the PGSC ( Peromyscus Stock Center ). information is on the reproductive biology of Peromyscus , in both the laboratory and field ( 1989 ). are studies by ), ), Maddock and ), ), and ), and ), Nelson ), and Demas and others ). Many species of Peromyscus in captivity ( Dice 1933 ). breeding of P. maniculatus has been by and others ), ), ), and ), and and ), among , 1988 ) extensively investigated in breeding behavior of deer mice and other Peromyscus species. At the PGSC, reproductive of both wild-type and most mutant deer mouse stocks are ( Table 2 ). are by 50 days of The of the deer mouse is days ( ) and is except in for which is between 4 to days and to 27 is when animals are in breeding many other small about and will at this time ( and ). Thus, are at to of the are 3 or in under natural The number is of which or more are to to The number ranges from 3 to and weight for is in laboratory stocks of Peromyscus on 20 that or more for stock. that 1 or more from among 100 or more for stock. interval 1 when are at For are and remain as long as they are be for and are not in Peromyscus and are not a of are during A is and a to is will are by the to and in to a The be with the In some the to of the young ( Gubernick and others 1994 ; and 1991 ). of a to a the ( and ; 1985 ). be from the breeding when they are 25 days Although they as as 20 days for another several days to and It is to the young at this The animals are to by until for It is to mating with a to a record of breeding of deer mice for 3 be to other the syndrome in which a but consistently to or The syndrome is when the to a and the at the nest and the about the and when is of in the of the The young are typically approximately 1 of this not as However, a will and a particularly when but It is important to distinguish between these 2 Deer mice and Peromyscus are easily maintained using standard laboratory mouse A of animals are in and are laboratory rodent is by the or be and be of and are and be for be Deer mice are but The is to of or other be A small of be as but is not and probably breeding only be used for since some animals will and from and be Deer mice and other Peromyscus species are typically and disease in They consistently for common murine years of with large of deer mice, have experienced only 1 that in In approximately deer mice in the during a A of 60 laboratory ( Rattus norvegicus ) in an animal experienced during this same P. maniculatus were primarily and and were Although the pathogen was was to be ( or ), from from an greatly animal and of Peromyscus from other has been another major disease at the deer mice, particularly when When this is the animals be isolated and to the until the which occur in deer mice, can be controlled with and other are a in a animal they of the with the Wild Peromyscus mice are as carriers of and the larval tick of Lyme disease and other human animals be in and from Wild Peromyscus be handled with The for and has for handling rodents ( and others ). Deer mice with and remain The of of is not but be by Peromyscus from other be isolated until to that animals are deer mice from by the for and of Animal Care little of disease to and However, some and to deer mice and with Deer mice are more active than laboratory house mice and will readily not properly A handling with a is Although the animals will bite handled they bite handling with than with is The animals to The at the is and the animals be by the of the Deer mice also be by the of the the and the animal by the For or other the animals can be by the animal by the of the between the and of the for and the tail between the and of the same The is to a or other or to record used for laboratory mice well for deer mice. and are the At the PGSC, is used with is by using Although Peromyscus not as or under animal animal are those to laboratory Mus and Rattus Peromyscus are subject to by the Department of at Peromyscus are more active at than during the of behavior is greater than that of laboratory mice ( ), and they many and of and all of which are individuals will readily of information is in the literature on the of deer mice and other Peromyscus species. body metabolism and of are by and ). body in studies for subspecies of deer mouse average The based on these studies for the deer mouse is to of of averages for subspecies of P. maniculatus , a than that in various species to for laboratory stocks of Peromyscus are in Table 3 for laboratory stocks of Peromyscus 2 in ; ; not information is also for the deer mouse. recent have been studies of reproductive are those of and ), and ), and others ), Demas and others ), and ), and ). function ( and others 1985 ; and others ), effects on metabolism ( and 1988 ; and ), and and other ( and 1988 ; and others 1994 ; and 1990 ) are in the and in many literature also on alcohol to environmental and other aspects of metabolism and in deer mice and related Peromyscus species. The at the PGSC has several these are (1) to the genetics, physiology, and of the most widely used standard deer mouse (2) to mutant strains for the genetic by using of morphological and biochemical to inbred strains of Peromyscus These are under at the University of South Carolina and at the time of this One widely used Washtenaw or has in captivity for 50 In a breeding stock was initiated from wild deer mice of the prairie subspecies ( P. m. bairdii ) in Washtenaw Michigan. This stock proved to be and to well in It has been maintained as a stock at several since with a to the The stock to the of the animals, thus as a standard This stock has been utilized in numerous behavioral, and genetic studies. Because of fertility and also is to improve of various mutant The reproductive of this and 2 other “wild-type” stocks of Peromyscus are in Table 2 At the time of this writing, 25 mutant of deer mice are maintained in the PGSC ( Table 4 ). of these represent distinctive coat color and but other morphological including 2 are in the Additionally, several mutants are that and The and variants have research variants of deer mouse maintained by the Peromyscus Genetic Stock Center or where in The deer mouse will in captivity to the mouse ( Peromyscus ), a more species from the United to ( Dawson ). However, this is only when the deer mouse is used as the of both are as in either as either These have proved useful in studies of ( and others 1983 ; and Dawson ) and size ( Dawson ; Dawson and others 1993 ) and for genetic ( Dawson and others 1983 ). Deer mice and their allies Peromyscus ) are a and of rodents in North America. bred stocks of and variant of the genus have in both and research. The PGSC at the University of South Carolina has an active to these animals as a research for the scientific community at The Peromyscus Genetic Stock Center is supported in part by National Science Foundation The Peromyscus Genetic is supported in part by also and the numerous investigators through the years since have with the Stock