Studies reviewed include the following: In addition to mating preference and the Y maze, a new test system was introduced which depends on the blocking of preganancy in females experiencing the scent of a non-stud male and involves an adverse neuroendocrine response to olfactory recognition of identity. The higher incidence of terminated pregnancy observed when the genetic difference between stud and non-stud males was confined to the Major Histocompatibility Complex (MHC), or to a mutated H-2K gene, signifies further reproductive consequences of MHC- related chemosensory individuality and, together with distinctions of urines of H-2K mutant mice in the Y maze, identifies one class of MHC genes, class I, involved in individual odor constitution. An automated, computed-programmed olfactometer was build and used to show that rats recognize the MHC-related odor differences of mice. Some human subjects also can make this distinction. The odor of F1 progeny of MHC-congenic crosses is characteristic of MHC heterozygosity, in addition to codominant characteristics of the two inbred parents. Testing of radiation chimeras whose donor cells express a non-host MHC haplotype showed that hematopoietic cells are one source of MHC-related odorants. To simplify the comparison of volatile compound of differing MHC origins in combined gas chromatography and mass spectrometry, we focused on H-2Kb vs. H-2Kbm1 and found a significant quantitative difference in a major volatile consistent with 2-sec-butyl-2-thiazoline. Regarding non-MHC genes, the X and Y chromosomes were shown to confer odor individuality indicative of genotype. Maternal mitochondrial differences of reciprocal hybrids of uniform nuclear genotype were not distinguished. Disparities confined to non-MHC autosomal segments are distinguished, if at all, only with exceptional difficulty.
Aims proposed are directed to logical extensions of these findings and to other outstanding aspects, namely inquiry into the relation of MHC-related mating preference and differential effects on pregnancy to chemical imprinting on maternal and familial MHC types; contributions of non- hematopoietic cells to MHC odor constitution; milk and other non-urinary fluids as sources of MHC odorants; volatile-carrier functions of urinary class I MHC derivations; influence of oncogenic retroviruses in various modes with respect to the host, and of ensuing jpre-malignancy and malignancy; and communication of MHC identity among freely segregating populations, preparatory to study of human MHC (HLA) distinctions by rats in the automated olfactometer.

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National Institute of General Medical Sciences (NIGMS)
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Mammalian Genetics Study Section (MGN)
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Monell Chemical Senses Center
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Singer, A G; Beauchamp, G K; Yamazaki, K (1997) Volatile signals of the major histocompatibility complex in male mouse urine. Proc Natl Acad Sci U S A 94:2210-4
Beauchamp, G K; Katahira, K; Yamazaki, K et al. (1995) Evidence suggesting that the odortypes of pregnant women are a compound of maternal and fetal odortypes. Proc Natl Acad Sci U S A 92:2617-21
Beauchamp, G K; Yamazaki, K; Curran, M et al. (1994) Fetal H-2 odortypes are evident in the urine of pregnant female mice. Immunogenetics 39:109-13
Yamazaki, K; Beauchamp, G K; Shen, F W et al. (1994) Discrimination of odortypes determined by the major histocompatibility complex among outbred mice. Proc Natl Acad Sci U S A 91:3735-8
Monahan, E; Yamazaki, K; Beauchamp, G K et al. (1993) Olfactory discrimination of urinary odortypes from congenic strains (DBA/1Bg and DBA1.C57BL10-YBg) of mice differing in their Y chromosomes. Behav Genet 23:251-5
Yamazaki, K; Beauchamp, G K; Imai, Y et al. (1992) Expression of urinary H-2 odortypes by infant mice. Proc Natl Acad Sci U S A 89:2756-8
Yamazaki, K; Beauchamp, G K; Shen, F W et al. (1991) A distinctive change in odortype determined by H-2D/L mutation. Immunogenetics 34:129-31
Yamazaki, K; Beauchamp, G K; Imai, Y et al. (1990) Odor types determined by the major histocompatibility complex in germfree mice. Proc Natl Acad Sci U S A 87:8413-6
Yamazaki, K; Beauchamp, G K; Bard, J et al. (1989) Sex-chromosomal odor types influence the maintenance of early pregnancy in mice. Proc Natl Acad Sci U S A 86:9399-401
Beauchamp, G K; Yamazaki, K; Bard, J et al. (1988) Preweaning experience in the control of mating preferences by genes in the major histocompatibility complex of the mouse. Behav Genet 18:537-47

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