A Quantitative Trait Locus in Major Histocompatibility Complex Determining Latent Period of Mouse Lymphomas

Shisa, Hayase; Pataer, Abujiang; Lu, Ling; Yoshida, Osamu; Yamada, Yoshihiro; Hayashi, Hiroshi

doi:10.1111/j.1349-7006.1996.tb00236.x

Cited by 8 publications

(4 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Effect of MHC loci on lymphoma latency is controversial in mouse models (Lilly and Pincus, 1973;Chen and Lilly, 1982;Mucenski et al, 1986;Vasmel et al, 1988;Kamoto et al, 1996). Resistance to virus or tumour cells by the immune system is regulated by class II MHC loci.…”

Section: Discussionmentioning

confidence: 99%

Propylnitrosourea-induced T-lymphomas in LEXF RI strains of rats: genetic analysis

Shisa

Tanuma

et al. 1999

Br J Cancer

View full text Add to dashboard Cite

Our recent studies have shown that types of lymphomas and leukaemias are determined by host genes in certain experimental models (Yamada et al, 1994a(Yamada et al, , 1994b. Propylnitrosourea (PNU)-induced T-lymphomas are one such example. F344 rats exhibit high susceptibility, whereas many other strains of rats develop predominantly erythro-or myeloid leukaemias (Shisa and Hiai, 1985;Shisa and Suzuki, 1991) We have assumed that a single dominant gene of F344 rats determines the susceptibility to T-lymphomas and that another independently segregating dominant gene determines the length of the latency period (Shisa and Hiai, 1985). Subsequent efforts to map such genes with crosses between F344 and LE rats, however, have met with great difficulty (Shisa et al, unpublished observation). The difficulty seems to arise partly from paucity of rat genetic marker at that time and partly because these traits are quantitative in nature and mutigenic, rather than a single gene inheritance.The recombinant inbred (RI) strains represent a set of stable inbred strains derived from F2 intercross between two parental inbred stains. The RI strains are extremely useful for the genetic analysis of complex traits (Taylor, 1978;Bailey, 1981). To analyse T-lymphoma susceptibility, we have established a new set of rat RI strains, LEXF, from matings between F344 and LE/Stm strains rats. The LEXF RI strains comprise 11 independent strains and 13 of their sublines. The strain distribution pattern (SDP) of LEXF has been extensively analysed (Shisa et al, 1997;Lu et al, 1998).In this paper, we report the PNU-induced carcinogenesis in the LEXF RI strains, and survey the host genes responsible for determination of the disease types and length of the latency period calculated using quantitative trait locus (QTL) analysis with the Map Manager QT software developed by Manly (1993). We found that numerous QTL with opposed functions are involved in determining the types of lymphomas and latency periods. To control type I and type II errors (Belknap et al, 1992(Belknap et al, , 1996, we further evaluated these putative loci in 137 backcross generation of (F344 × LE)F1 × LE rats. Significant linkage with T-lymphomagenesis was confirmed for three loci on chromosome 5, 7 and 10 and suggestive linkage, for a locus on chromosome 1. MATERIALS AND METHODS AnimalsThe LE/Stm rats were originally derived from a closed colony of Long-Evans rats at Ben May Laboratory, University of Chicago (Chicago, IL, USA) and maintained at Saitama Cancer Center Research Institute by brother-sister matings for > 50 generations. The F344 rats were derived from a pair of F344/DuCrj rats purchased from Charles River Japan, Inc. (Kanagawa, Japan) and thereafter maintained by brother-sister matings for > 23 generations. The LEXF was a set of 11 independent RI strains and 13 sublines (Shisa et al, 1997) In this study all LEXF RI strains except for LEXF 6B, a poor breeder, were used. These sublines were branched out at the 7th to 11th generations after an attempt to fix coat colour. ...

show abstract

Section: Discussionmentioning

confidence: 99%

Propylnitrosourea-induced T-lymphomas in LEXF RI strains of rats: genetic analysis

Shisa

Tanuma

et al. 1999

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…21) Homozygotes of the SL/Kh allele at D17Mit21 have a significantly shorter latent period than individuals with the AKR allele (P<0.0001). This locus is called Lla1 (Lymphoma latency acceleration-1).…”

Section: Host Factors Affecting Lymphomagenesismentioning

confidence: 97%

“…Among lymphomas in (SL/Kh×AKR)F2, the length of latency is apparently related not to the type of lymphoma, but to the allele of the major histocompatibility locus. 21) Homozygotes of the SL/Kh allele at D17Mit21 have a significantly shorter latent period than individuals with the AKR allele (P<0.0001). This locus is called Lla1 (Lymphoma latency acceleration-1).…”

Section: Host Factors Affecting Lymphomagenesismentioning

confidence: 97%

Pre‐B lymphomas in SL/Kh mice: A multifactorial disease model

2003

Self Cite

View full text Add to dashboard Cite

The pre-B lymphoma in the inbred mouse strain SL/Kh is an excellent multifactorial disease model. The endogenous murine leukemia virus provirus Emv11, genetically acquired from an AKR progenitor, is the pathogenetic agent that reintegrates to dysregulate several host genes, i. pontaneous pre-B lymphoma is a relatively rare category among mouse lymphoid neoplasias. 1) We have established the SL/Kh strain mice, which has an extremely high incidence of pre-B lymphomas with short latency induced by endogenous murine leukemia virus (MuLV).2, 3) Studies on SL/Kh mice for a quarter of century have revealed that they provide an excellent multifactorial disease model. In this article, we will review the origin of the SL/Kh strain, the pathology, virology, and molecular mechanism of lymphomagenesis, the genetic and epigenetic determination of types, and the latency of diseases.

show abstract

“…Likewise, the F 1 between FVB (H-2q) and TG-B also developed cancer at a reduced rate. In fact, the H-2 region has been shown to contain a major modifier for susceptibility to lymphoma (Kamoto et al, 1996).…”

mentioning

confidence: 99%

Development of a Novel Prognostic Marker to Link a Potential Tumor Suppressor Gene at Chromosome 6q to Aberrant Signal Transduction Pathway in Breast Cancer

Zheng¹

2005

View full text Add to dashboard Cite

Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send Comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information ABSTRACT This is the final report on the grant "Development of a novel diagnostic marker to link a potential tumor suppressor gene at chromosome 6q to aberrant signal transduction pathway in breast cancer". The purpose of the grant proposal is to examine the hypothesis that protein phosphatase laforin is a tumor suppressor in cancers through its function as the specific phosphatase of GSK-3[3 and the loss of function of laforin causes aberrant Wnt signaling in cancer cells. We have proposed to examine (1) whether the specific marker is present in breast cancer cells; (2) whether the unique morphological marker correlates with specific LOH in 6q24; (3) whether there are inactivating mutations in laforin gene; (4) whether loss of laforin function in breast cancer cells causes downstream effects on 3-catenin cytosolic and nuclear accumulation and increased cyclin D and c-myc expression in breast cancer samples. (5) Finally, we will examine whether loss of laforin function in breast cancer cells is an independent prognostic factor. In the past funding period, we have greatly extended our work in basic research to firmly establish the role of laforin as a tumor suppressor. First, we showed that silencing the Epm2a gene (which encodes laforin) in the bone marrow stem cells resulted in a dramatic increase in the self-renewal of the hematopoietic stem cells in methylcellulose assay in vitro and in the tendency for hematological malignancy transformation in vivo. Second, we have demonstrated that abnormal Wnt signaling associated with laforin down-regulation is a causal event for the malignant transformation mediated by laforin-down regulation.Principal Investigator: Pan ZhenZ, MD, PhD

show abstract

A Quantitative Trait Locus in Major Histocompatibility Complex Determining Latent Period of Mouse Lymphomas

Cited by 8 publications

References 15 publications

Propylnitrosourea-induced T-lymphomas in LEXF RI strains of rats: genetic analysis

Propylnitrosourea-induced T-lymphomas in LEXF RI strains of rats: genetic analysis

Pre‐B lymphomas in SL/Kh mice: A multifactorial disease model

Development of a Novel Prognostic Marker to Link a Potential Tumor Suppressor Gene at Chromosome 6q to Aberrant Signal Transduction Pathway in Breast Cancer

Contact Info

Product

Resources

About