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1.  Genomic organization and phylogenetic utility of deer mouse (Peromyscus maniculatus) lymphotoxin-alpha and lymphotoxin-beta 
BMC Immunology  2008;9:62.
Deer mice (Peromyscus maniculatus) are among the most common mammals in North America and are important reservoirs of several human pathogens, including Sin Nombre hantavirus (SNV). SNV can establish a life-long apathogenic infection in deer mice, which can shed virus in excrement for transmission to humans. Patients that die from hantavirus cardiopulmonary syndrome (HCPS) have been found to express several proinflammatory cytokines, including lymphotoxin (LT), in the lungs. It is thought that these cytokines contribute to the pathogenesis of HCPS. LT is not expressed by virus-specific CD4+ T cells from infected deer mice, suggesting a limited role for this pathway in reservoir responses to hantaviruses.
We have cloned the genes encoding deer mouse LTα and LTβ and have found them to be highly similar to orthologous rodent sequences but with some differences in promoters elements. The phylogenetic analyses performed on the LTα, LTβ, and combined data sets yielded a strongly-supported sister-group relationship between the two murines (the house mouse and the rat). The deer mouse, a sigmodontine, appeared as the sister group to the murine clade in all of the analyses. High bootstrap values characterized the grouping of murids.
No conspicuous differences compared to other species are present in the predicted amino acid sequences of LTα or LTβ; however, some promoter differences were noted in LTβ. Although more extensive taxonomic sampling is required to confirm the results of our analyses, the preliminary findings indicate that both genes (analyzed both separately and in combination) hold potential for resolving relationships among rodents and other mammals at the subfamily level.
PMCID: PMC2605436  PMID: 18976466
2.  Profiling helper T cell subset gene expression in deer mice 
BMC Immunology  2006;7:18.
Deer mice (Peromyscus maniculatus) are the most common mammals in North America and are reservoirs for several zoonotic agents, including Sin Nombre virus (SNV), the principal etiologic agent of hantavirus cardiopulmonary syndrome (HCPS) in North America. Unlike human HCPS patients, SNV-infected deer mice show no overt pathological symptoms, despite the presence of virus in the lungs. A neutralizing IgG antibody response occurs, but the virus establishes a persistent infection. Limitations of detailed analysis of deer mouse immune responses to SNV are the lack of reagents and methods for evaluating such responses.
We developed real-time PCR-based detection assays for several immune-related transcription factor and cytokine genes from deer mice that permit the profiling of CD4+ helper T cells, including markers of Th1 cells (T-bet, STAT4, IFNγ, TNF, LT), Th2 cells (GATA-3, STAT6, IL-4, IL-5) and regulatory T cells (Fox-p3, IL-10, TGFβ1). These assays compare the expression of in vitro antigen-stimulated and unstimulated T cells from individual deer mice.
We developed molecular methods for profiling immune gene expression in deer mice, including a multiplexed real-time PCR assay for assessing expression of several cytokine and transcription factor genes. These assays should be useful for characterizing the immune responses of experimentally- and naturally-infected deer mice.
PMCID: PMC1559719  PMID: 16916450
3.  Generation of competent bone marrow-derived antigen presenting cells from the deer mouse (Peromyscus maniculatus) 
BMC Immunology  2004;5:23.
Human infections with Sin Nombre virus (SNV) and related New World hantaviruses often lead to hantavirus cardiopulmonary syndrome (HCPS), a sometimes fatal illness. Lungs of patients who die from HCPS exhibit cytokine-producing mononuclear infiltrates and pronounced pulmonary inflammation. Deer mice (Peromyscus maniculatus) are the principal natural hosts of SNV, in which the virus establishes life-long persistence without conspicuous pathology. Little is known about the mechanisms SNV employs to evade the immune response of deer mice, and experimental examination of this question has been difficult because of a lack of methodologies for examining such responses during infection. One such deficiency is our inability to characterize T cell responses because susceptible syngeneic deer mice are not available.
To solve this problem, we have developed an in vitro method of expanding and generating competent antigen presenting cells (APC) from deer mouse bone marrow using commercially-available house mouse (Mus musculus) granulocyte-macrophage colony stimulating factor. These cells are capable of processing and presenting soluble protein to antigen-specific autologous helper T cells in vitro. Inclusion of antigen-specific deer mouse antibody augments T cell stimulation, presumably through Fc receptor-mediated endocytosis.
The use of these APC has allowed us to dramatically expand deer mouse helper T cells in culture and should permit extensive characterization of T cell epitopes. Considering the evolutionary divergence between deer mice and house mice, it is probable that this method will be useful to other investigators using unconventional models of rodent-borne diseases.
PMCID: PMC524361  PMID: 15458574
4.  Cloning and characterization of deer mouse (Peromyscus maniculatus) cytokine and chemokine cDNAs 
BMC Immunology  2004;5:1.
Sin Nombre virus (SNV) establishes a persistent infection in the deer mouse, Peromyscus maniculatus. A strong antibody response occurs in response to SNV infection, but the role of the innate immune response is unclear. To address this issue, we have initiated an effort to identify and characterize deer mouse cytokine and chemokine genes. Such cytokines and chemokines are involved in various aspects of immunity, including the transition from innate to adaptive responses, type I and type II responses, recruitment of leukocytes to sites of infection, and production of mature cells from bone marrow progenitors.
We established a colony of SNV antibody-negative deer mice and cloned 11 cytokine and chemokine partial cDNA sequences using directed PCR. Most of the deer mouse sequences were highly conserved with orthologous sequences from other rodent species and functional domains were identified in each putative polypeptide.
The availability of these sequences will allow the examination of the role of these cytokines in deer mouse responses to infection with Sin Nombre virus.
PMCID: PMC331403  PMID: 14720307

Results 1-4 (4)