This project has two basic objectives. The first is to conduct a final screening program specifically aimed at the recovery of H-2 mutations which can answer basic questions about the process(es) which have been implicated in their generation. The second is to continue meeting requests from other investigators for mutants and, over the course of the project period, to phase out the active breeding and culminate with the preservation of the mutants in a frozen embryo bank. Most, if not all, of the in vivo H-2 mutations have characteristics which have been interpreted to imply their generation via a process involving transfers of DNA sequences between non-allelic genes (micro-recombination or """"""""gene conversion"""""""" rather than relying on simply the accretion of single base changes. One of the basic pieces of information missing for the modeling/testing of such a process is whether such transfers can definitively be attributed to cis-(within-single chromosomes) or trans (between homologous chromosomes) configurations. This project proposes a limited and directed screening program to attempt to identify H-2 mutation-s which can definitively be attributed to cis or to trans """"""""gene conversions"""""""". Such an search is unlikely to occur elsewhere. Actual demonstration of such events will facilitate the analysis of this process which is thought by many to be important in the in vivo generation of diversity within the MHC. This project also proposes to continue the maintenance of a colony of mice bearing H-2 histocompatibility gene mutations as a resource colony. New mutants may be added, if and as they become available. Maintained strains will be systematically monitored by skin grafting to ensure their genetic integrity. The current frequency of requests suggests that an actively breeding colony is still justifiable to expeditiously fulfill the requests. However the phasing out of the breeding colony, and its entry into a frozen embryo bank(s), is planned in order to accommodate the P.I.'s future plans.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI016919-15
Application #
3126901
Study Section
Immunobiology Study Section (IMB)
Project Start
1979-09-01
Project End
1995-08-31
Budget Start
1993-09-01
Budget End
1994-08-31
Support Year
15
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Type
Schools of Dentistry
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Wang, K; Busker-Mannie, A E; Hoeft, J et al. (2001) Prolonged Hya-disparate skin graft survival in ethanol-consuming mice: correlation with impaired delayed hypersensitivity. Alcohol Clin Exp Res 25:1542-8
Yun, T J; Melvold, R W; Pease, L R (1997) A complex major histocompatibility complex D locus variant generated by an unusual recombination mechanism in mice. Proc Natl Acad Sci U S A 94:1384-9
Makino, M; Murphy, D B; Melvold, R W et al. (1995) Impact of MHC class I gene on resistance to murine AIDS. Scand J Immunol 42:368-72
Rubocki, R J; Connolly, J M; Hansen, T H et al. (1991) Mutation at amino acid position 133 of H-2Dd prevents beta 2m association and immune recognition but not surface expression. J Immunol 146:2352-7
Busker, A E; Miller, S D; Melvold, R W (1990) Induction of allograft tolerance to the H-Y antigen in adult C57BL/6 mice: differential effects on delayed-type hypersensitivity and cytolytic T-lymphocyte activity. Cell Immunol 125:225-34
Melvold, R W; Jokinen, D M; Miller, S D et al. (1990) Identification of a locus on mouse chromosome 3 involved in differential susceptibility to Theiler's murine encephalomyelitis virus-induced demyelinating disease. J Virol 64:686-90
Melvold, R W; Jokinen, D M; Knobler, R L et al. (1987) Variations in genetic control of susceptibility to Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease. I. Differences between susceptible SJL/J and resistant BALB/c strains map near the T cell beta-chain constant gene on chromos J Immunol 138:1429-33
Colombo, M P; Melvold, R W; Wettstein, P J (1987) Inheritance of a mutant histocompatibility gene and a new mammary tumor virus genome in the B6.KH-84 mouse strain. Immunogenetics 26:99-104
Stuart, P M; Iannaccone, P M; Miller, S D et al. (1987) In vitro and in vivo correlates of hybrid tumor resistance. J Natl Cancer Inst 78:1159-68
Wettstein, P J; Melvold, R W (1986) Xenotropic virus-related restriction patterns of non-H-2 histocompatibility mutant mice strains. Immunogenetics 23:156-63

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