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Of 8 Thoroughbred foals in which osteochondrosis developed before weaning, 7 had serum copper and ceruloplasmin concentrations below normal. Three foals on one farm had serum zinc content high enough to suggest zinc toxicosis, and the liver of each foal contained abnormally high content of zinc. Four foals from the second farm had extremely low serum copper content, but normal serum zinc content. Evidence of environmental exposure to excess zinc was not found on either farm. The lesions in the zones of endochondral ossification of the afflicted foals were similar in many respects to those found in other species of animals with molybdenum-induced copper deficiency and with inhibition of the function of copper-dependent lysyl oxidase by beta-aminopropionitrile, a toxic component of Lathyrus odoratus known to cause osteolathyrism.

The endogenous neuraminidase activity of various mouse lymphoid subpopulations and tissue compartments was examined by a sensitive fluorometric assay. These analyses indicated that activated T lymphocytes possessed a significantly higher level of intracellular neuraminidase than activated B or resting T or B lymphocytes. Examination of the level of neuraminidase in bone marrow, thymus, lymph node, and unfractionated spleen indicated that these lymphoid tissues contained significantly less neuraminidase than was detected in stimulated T cells. Kinetic studies revealed that the majority of the increase in neuraminidase activity occurred between 24 and 48 h following stimulation. Analysis of activated T lymphocytes prepared from a panel of inbred mouse strains indicated that cells from mice of the H-2v haplotype, which possess the Neu-1a allele and are deficient in liver neuraminidase, exhibited a level of activity which was significantly lower than that detected in stimulated T cells from other mouse strains. These results indicate that the endogenous neuraminidase activity of T lymphocytes increases upon stimulation, and that the level of this enzyme activity in lymphoid cells is also controlled by the Neu-1 locus, which is located in the H-2 region of the major histocompatibility complex.

Electrophoretic variation for an intestinal enzyme that cleaves L-leucyl-beta-naphthylamide has been discovered among inbred mouse strains. Several strains including related strains C57BL/6J, C57BL/10J, C57BR/cdJ, C57L/J, and C58/J demonstrate an electrophoretic band of this enzyme that is absent in other strains and stocks thus far observed. The enzyme is tentatively being called leucine arylaminopeptidase (LAP) and the variant genetic locus Lap-1. The presence of the band is determined by an allele designated Lap-1a. Homozygotes for the alternate allele, Lap-1b, are without the band and heterozygotes are, under our electrophoretic conditions, indistinguishable from Lap-1a homozygotes. Data from recombinant inbred lines and a B6D2F1 X DBA/2J backcross established linkage of Lap-1 to dilute (d) and supernatant malic enzyme (Mod-1) on chromosome 9 in the following order: Lap-1-d-Mod-1. The Lap-1 to d map distance was estimated to be 21.3 +/- 4.6 cM from backcross data and 8.1 +/- 4.8 cM from recombinant inbred lines.

The relationship of B cell hyperactivity and retrovirus expression to other autoimmune traits were examined in recombinant inbred (N X 8 RI) lines derived from NZB and C58 progenitor strains. Although both NZB and C58 mice expressed high levels of xenotropic virus, the RI lines segregated in virologic phenotype, as high or low expressors of the endogenous virus. The expression of the C58-derived ecotropic virus occurred in only one-half of the RI lines, and its expression in the remaining lines of mice appeared to be suppressed by the NZB-derived allele at the Fv-1 locus. The inheritance of B lymphocyte abnormalities of the NZB progenitor strain was investigated by studying spontaneous and SRBC-induced production of IgM by the spleen cells of the RI lines. These two phenotypes of B cell hyperactivity were found to be determined by independently segregating genes and they were not linked to immunoglobulin structural gene loci. The strain distribution patterns of virus expression and B cell hyperactivity in the RI lines did not match with each other or with the inheritance patterns of other immunologic abnormalities, such as defective AMLR and production of autoantibodies.

Genes for fibronectin, gamma crystallin, and isocitrate dehydrogenase-1 are syntenic in mouse, man, and cow. In an effort to physically locate this conserved chromosome region in the genomes of the respective species, we have localized the fibronectin and gamma crystallin genes to mouse chromosome 1, region C1-5 by in situ hybridization. In situ hybridization was conducted on metaphase chromosomes of bone marrow preparations of Rb 1.7 mice. These cells contain Robertsonian translocated chromosomes 1 and 7 as the only submetacentric chromosome in an otherwise acrocentric genome. Physically mapping these genes to mouse chromosome 1 now enables comparisons of the genetic map and the physical map on the proximal half of this chromosome. Genes in this conserved region of mouse chromosome 1 are also involved in resistance to intracellular pathogens, and the chromosomal localization of this region may facilitate the identification of homologous genes in other species.

An ethylnitrosourea (ENU)-induced electrophoretic variant of mouse PEP-2, a tripeptidase, has been used to determine the location of the structural gene on chromosome 10. Gene order and recombination frequencies were estimated as Apk-21.8 +/- 3.9%-Pep-2-3.7 +/- 2.1%-Sl. Methods for rapid determination of Apk and Pep-2 alleles by cellulose acetate electrophoresis and a valuable linkage testing stock carrying the unique Apkm and Pep-2b alleles are described.

DNA from bovine x hamster hybrid cells preferentially segregating bovine chromosomes has been analyzed by blot hybridization with alpha and beta interferon probes. Retention or loss of bovine interferon genes was compared to segregation of bovine isozyme loci representing previously described syntenic groups. Families of bovine alpha (IFNA) and beta (IFNB) interferon genes were segregated in concordance with each other and with aconitase-1 (ACO1) on bovine syntenic group U18. This syntenic relationship is conserved on human chromosome 9p and on the portion of mouse chromosome 4 proximal to the centromere. In addition, cattle restriction fragment length polymorphisms were identified with both IFNA and IFNB probes. Of particular interest is a polymorphism apparently due to duplication of IFNB genes.

Genetic variation among inbred strains is described for electrophoretic migration of alkaline phosphatase from intestine, kidney, blood plasma, and three isozymes of liver. A manganese-requiring isozyme of liver and kidney unaffected by neuraminidase is described, and the locus controlling variation in this isozyme is designated Akp-1. Data from recombinant inbred strains place the locus on chromosome 1 at a distance of 3.6 +/- 2.9 cM from the M1s locus on the side distal to the centromere. Test-cross data show the following gene order and recombination percentages: Dip-1 19.0 +/- 3.8% Lp 7.4 +/- 2.2% Akp-1.

Uridine blocks the in vivo conversion of thymine to thymidine in Escherichia coli, thus, one can change DNA labels by labelling first with a thymine label (e.g. 14C) and then, at the time of the change, adding 50 microgram uridine per ml and thymidine (e.g. 3H). The cells immediately start using the thymidine, ignore the thymine for several generations, and are not affected by the uridine.

Much of the total genomic variation in eukaryotic organisms may be due to genes other than those coding the primary translation product. Allelic variation, especially as detectable by electrophoresis, in the post-translational processing of enzymes has been briefly reviewed with considerable attention given to a mouse gene (Neu-1) and its pleiotropic effects on several lysosomal hydrolases. Liver acid phosphatase, alpha-mannosidase, arylsulfatase B, and alpha-glucosidase are differentially sialylated as the result of allelic variation for a gene controlling liver neuraminidase activity. Strain SM/J has only 15-20% of the total neuraminidase activity of control strains and is almost totally deficient in the more heat labile of two components of liver activity. The locus controlling this variation (Neu-1) maps very near the D end of H-2 on chromosome 17, apparently within the S region of H-2. A homologous gene has been mapped near the MHC of the rat. The exact nature of the mouse mutant and its relationship to several human diseases characterized by neuraminidase deficiency has not been determined.

Classical cytogenetics has been merged with somatic cell and molecular genetics to facilitate mapping of the bovine genome. A physical map is presently being generated by the use of hybrid somatic cells and in situ hybridization to assign genes to chromosomes. A complementary genetic map is being generated by analysis of recombination of polymorphic loci, many of them identified with the same cloned DNA probes used for physical mapping. The eventual utilization of this map for selective breeding of disease resistance and productivity is dependent on the saturation of the map with polymorphic markers at a density that will assure linkage of genes influencing desirable phenotypes with at least one polymorphic marker. The identification of regions of chromosomal conservation among cattle, mice, and humans is being exploited to facilitate the saturation of the bovine map with useful markers.

Electrophoretic variants of two carbonic anhydrase enzymes CAR-1 (CA I) and Car-2 (CA II), have been found in the laboratory mouse, Mus musculus. These two loci are closely linked to each other and are located on chromosome 3 near its centromere. The close linkage of Car-1 and Car-2 supports the hypothesis that the present-day carbonic anhydrase loci are the result of tandem duplication of an earlier carbonic anhydrase locus with subsequent divergence. The red blood cells of mice of the subspecies M.m. casteneus have significantly reduced levels of CAR-1 and CAR-2.

Three alleles at the Gpt-1 (glutamic-pyruvic transaminase-1) locus in the mouse, as identified by electrophoresis on cellulose acetate, and their distribution among inbred mouse strains and wild stocks are described. The Gpt-1 locus was shown to control the soluble form of the enzyme. Three-point linkage analysis established th location of Gpt-1 on chromosome 15 between uw and bt. In addition, a new staining procedure is described that allows the visualization of GPT activity on gels by the deposition of formazan. This is an improvement over previous methods that produced bands of nonfluorescence against a fluorescent background.

The genes encoding bovine prolactin and rhodopsin were assigned to syntenic groups on the basis of hybridization of DNA from a panel of bovine-hamster hybrid somatic cell lines with cloned prolactin and rhodopsin gene probes. Prolactin was found to be syntenic with previously mapped glyoxalase, BoLA and 21-hydroxylase genes, establishing a syntenic conservation with human chromosome 6. The presence of bovine rhodopsin sequences among the various hybrid cell lines was not concordant with any gene previously assigned to one of the 23 defined autosomal syntenic groups. Thus, rhodopsin marks a new bovine syntenic group, U24, leaving only five cattle autosomes unmarked by at least one biochemical or molecular marker.

Starch gel electrophoresis and histochemical staining with L-leucyl-L-tyrosine have revealed genetic variation for dipeptidase in Rattus norvegicus. The tissue distribution, substrate specificity, and heterozygous expression as a monmeric protein suggest homology of the variant peptidase to human PEP-C and mouse Pep-3 (Dip-1). We propose Peptidase-3 (Pep-3) as a name for this autosomal locus in the rat. The allele responsible for slower (less anodal) electrophoretic migration is designated Pep-3a and is characteristic of strain ACI/Pit. A faster (more anodal) electrophoretic mobility is the product of the Pep-3b allele in strain F344/Pit. Twenty-five additional inbred strains carry Pep-3a and 16 others carry Pep-3b. Wild rats trapped in Pittsburgh were polymorphic for this locus. Alleles at Pep-3 segregated independently of c (linkage group I), a (linkage group IV), RT2 and Es-1 (linkage group V), h (linkage group VI), and RTI (linkage group VIII).

Cattle-hamster hybrid somatic cells segregating cattle chromosomes have been analyzed by cellulose-acetate electrophoresis for 28 enzyme gene products including the previously unassigned loci for GAPD, ITPA, ADA, ACO1, GDH, GUK, CAT, and GLO1. These 28 loci are organized into 21 independent syntenic groups bringing the composite bovine gene map to 35 loci on 24 syntenic groups. Thirty-two homologous genes now have been mapped in humans, mice, and cattle. Conservation of cattle and human linkage groups is evidenced by only three linkage discordancies among these 32 loci as contrasted to nine discordancies among the same loci in the human and mouse maps.

The linkage of the locus for conversion of albumin (Acf-1) has been established on chromosome 1 with the following gene order and recombination percentages: Id-1 19.3 +/- 5.2% Acf-1 4.2 +/- 1.7% Dip-1 18.4 +/- 4.2% Lp.

Apl, a gene involved in the processing of lysosomal acid phosphatase in mouse liver, has been mapped on Chromosome 17. The gene order and map distances in per cent recombination of the loci studied are T (20.6 +/- 3.4) Pgk-2 (7.4 +/- 2.2) Apl. Thus, Apl is at least 7 cM distal to H-2 on this chromosome. In addition, strain-specific allelic variants for Apl have been demonstrated on cellulose acetate gels, a quick and inexpensive method of electrophoresis.

Genetic polymorphism for a previously undescribed serum protein has been found among inbred strains of Mus musculus. The new serum protein locus, gene symbol Sep-1, has been located on Chromosome 9, gene order Lap-1--Sep-1--Mpi-1--d--Mod-1, by utilizing information obtained from 52 recombinant inbred strains together with standard genetic backcrosses. The strain distribution pattern for this locus, supernatant malic enzyme, and transferrin also on Chromosome 9, are given for 67 inbred strains. Because the genotype of SEP-1 can be determined for individual mice without killing them, Sep-1 is a very useful gene in linkage studies and experimental biology.

There is no scientific justification for the use of random-bred or outbred rodents in toxicological and carcinogenesis testing. The frequent desire for heterozygosity in a test population can best be met by using F1 hybrids of inbred progenitor strains. Extrapolation of animal data to humans will ultimately come through an understanding of cellular responses to carcinogenic and toxicological agents. Isogenic animal populations such as inbred strains, F1 hybrids, and the recently developed recombinant inbred lines are currently our best approach to resolving these mechanisms.

Aryl hydrocarbon (benzo[a]pyrene) hydroxylase inducibility by benzo[a]anthracene was studied in 29 somatic cell hybrid clones, developed by fusing mouse spleen or peritoneal cells from four different inbred strains with hypoxanthine phosphoribosyltransferase-deficient Chinese hamster E36 cells. Karyotype analysis plus 25 markers assigned to 16 autosomes and the X chromosome were examined. In 28 of the 29 clones, the presence or absence of inducibility is associated with the presence or absence, respectively, of mouse chromosome 17. Liver microsomal aryl hydrocarbon hydroxylase induction by 3-methylcholanthrene or benzo[a]anthracene was assessed in appropriate backcrosses with the Mus musculus molossinus, M. m. castaneus, MOR/Cv, PL/J, SM/J and DBA/2J inbred strains and in 13 NX8 recombinant inbred lines. Twenty-seven biochemical genetic markers representing all but four autosomes were tested for possible linkage with the hydroxylase inducibility, and no linkage was found. The hepatic Ah receptor was quantitated in 26 BXD recombinant inbred lines; the Ah phenotype did not match exactly any of the more than 70 genes with established strain distribution patterns representing 12 autosomes and at least five unlinked markers. It is concluded that a major gene controlling aryl hydrocarbon hydroxylase inducibility by benzo[a]anthracene is located on chromosome 17. Because there is no significant linkage with any of three biochemical markers in the upper third of the chromosome, we conclude that the inducibility gene is located in the distal 40% of mouse chromosome 17. Whether this trait represents the Ah locus, i.e., the gene encoding the cytosolic Ah receptor, will require further study.

The incidence of hydronephrosis was determined in nine production colonies of Crl:CD (SD) BR rats (CD rats). Kidneys from 3909 rats were examined and 79 (2.0%) had unilateral or bilateral hydronephrosis. A colony with a relatively high incidence of hydronephrosis (4.1%) was chosen for further study. In unselected rats from this colony the incidence in females (87/1882, 4.6%) was not significantly different from that in males (79/1862, 4.2%). In the same group of rats, hydronephrosis was observed most frequently in the right kidney only (2.3%), followed by bilateral involvement (1.2%) and the left kidney only (0.8%). By selection and inbreeding, the incidence of hydronephrosis was increased dramatically (to 33.6%) in two generations. Hydronephrosis in the CD rat appears to be a highly heritable trait, most likely involving more than one gene.

Our genetic knowledge of a species is reflected in the state of its gene map. Although still primitive, relative to the gene map of the mouse, great strides have been made in recent years in developing the gene map of the rat and nine linkage groups have now been defined. Mapping by conventional backcrossing methods has been supplemented with parasexual methods using somatic cell hybrids. Use of recombinant-inbred strains has contributed significantly to the development of the mouse map and the technique holds promise for the future expansion of the rat map. Of great interest are comparative gene mapping and the relationship of linkage groups of the rat to those of other species. At present the linkage groups of the rat and the mouse reflect a high degree of conservation. This is surprising since chromosome banding patterns of the two species show but 40% homology.

Restriction fragment length polymorphisms (RFLPs) were observed in BamHI-digested mouse DNA probed with a cDNA for human fibronectin. Analysis of the inheritance of fibronectin RFLPs in AKXD and SWXJ recombinant inbred strains of mice mapped the locus, Fn-1, to the midregion of mouse chromosome 1 about 4 cM distal from the loci encoding gamma-crystallins (Cryg). Loci homologous to genes in the centromeric third of mouse chromosome 1 are also syntenic in rats, humans, and cattle and may, therefore, mark a large conserved chromosomal segment of the mammalian genome.

Technological advances in the 1970s encouraged the mapping of homologous gene loci in different mammalian species, including mouse and man. One hundred eighty-five homologous loci have now been mapped in these two species. Conservation of linkage is sufficient to identify substantial segments of the two genomes that have been left intact since their divergence from a common ancestor. The recognition of these conserved segments allows experimental manipulation of mouse chromosomes or chromosomal regions to produce models of human chromosomal anomalies of medical importance. Comparative gene mapping has been extended beyond mouse and man and the genomes of some species, including domestic cattle, appear to be more highly conserved relative to humans than the mouse. Such species may be particularly useful in providing models of human chromosomal anomalies that cannot be duplicated in laboratory mice.

During rapid growth, the excretion of pyrimidines, predominantly uracil, is a common phenomenon in procaryotes and eucaryotes. In Escherichia coli, some K-12 strains excrete orotic acid and not uracil. This is caused by a mutation in the pyrF gene.

The genes for isocitrate dehydrogenase-1, fibronectin, and gamma-crystallin are syntenic in man, mouse, and cow. In an effort to assign this bovine syntenic group to a specific chromosome and to allow a cytological comparison of the conserved chromosomal region containing these genes in their respective species, we have localized the fibronectin and gamma-crystallin genes to bovine chromosome 8, region 1.1-1.4. This study incorporates the techniques of hybrid somatic cell analysis and in situ hybridization and the use of a Robertsonian-translocated marker chromosome from a related species for regional assignment of genes to a specific bovine chromosome. The regions on human chromosome 2q, mouse chromosome 1, and cow chromosome 8 that contain these genes are cytologically similar, perhaps representing evolutionary conservation at the cytogenetic level as well as at the gene level for this group of loci.

A new esterase locus (Es-13) has been identified in Musculus. Strains AEJ/GnRk, LG/J, SJL/J, and SWR/J carry a recessive allele, Es-13b, for a locus possibly involved in the posttranslational modification of a kidney esterase. All other strains observed carried the dominant Es-13a allele. Es-13 was mapped on Chr 9 by recombinant inbred lines and by conventional backcrossing experiments. Backcross data produced the following gene order and map distances: Lap-1 (31.6 +/- 7.5 cM) Es-13 (2.6 +/- 2.6 cM) Mod-1.

A single formamidase, which is different from the formamidases found in other tissues occurs in the brains of mice. This enzyme is here called formamidase-5 and the gene symbol is designated For-5. Two alleles are recognized on the basis of their differential heat sensitivity:For-5b is relatively heat stable and is present in strain C57BL/6J, while For-5d is relatively heat sensitive and is present in strain DBA/2J. The heat sensitivity of formamidase-5 in 44 other inbred strains and substrains was tested and found to resemble that of C57BL/6J or DBA/2J. Thirty-six recombinant inbred strains derived from progenitors that differed at For-5 were studies to test for single-gene inheritance and linkage with other loci. Complete concordance was found with the esterase-10 locus (Es-10), indicating close linkage. The 99% upper confidence limit of the distance between For-5 and Es-10 is 3.7 centimorgans (cM). Es-10 is located on chromosome 14 about 19 cM from the centromere. An independent demonstration of linkage of For-5 with Es-10 and another chromosome 14 marker, hairless (hr), is provided by the finding that the HRS/J strain, which has been sibmated for 60 generations with forced heterozygosity at the hr locus, is cosegregating at For-5 and Es-10. A survey of 32 inbred strains and substrains revealed that the For-5d allele is associated with the Es-10b allele, and that the For-5b allele is associated with Es-10a and Es-10c. Formamidase-5 segregates as expected in the F2 generation of crosses between strains bearing For-5b and For-5d alleles. It is possible that this unique formamidase of the brain is involved in the metabolism of a neurotransmitter substance.

Two proto-oncogenes, Abl and Mos, have been physically localized on their respective mouse chromosomes by in situ hybridization. By means of Robertsonian translocations to facilitate chromosome identification, Abl was regionally assigned to 2B while Mos was assigned to 4A1-A2. Polymorphisms for these genes have not been reported in genomic DNA from standard inbred strains, nor were they found in this study, thereby prohibiting genetic mapping by meiotic recombination. These physical mapping data, however, extend the number of homologous genes assigned to chromosomal regions in both man and mouse, and better define the segments of conservation on mouse chromosome 2/human chromosome 9 and mouse chromosome 4/human chromosome 8, respectively.

We have isolated plasmids by linking the 5.9 MD EcoRI fragment of E. coli that carries the origin of replication to an EcoRI fragment that carries an amplicillin resistance determinant, but lacks an origin of replication. 3 plasmids of this type, pOC1, pOC2, and pOC3, are described in detail in this report. Although the plasmids have some adverse effect on the growth properties of the host strain, their existence shows that two functioning chromosomal origins can coexist in one cell. Deletions generated from this type of plasmids allow an allocation of the origin of replication of E. coli within a DNA segment less than 0.4 MD in size.

DNAs from cow-hamster and cow-mouse somatic hybrid cells segregating bovine chromosomes have been analyzed by Southern blotting and hybridization with human fibronectin and gamma crystallin probes. Concordancy of retention of these bovine genes was compared to cattle isozyme loci representing previously described syntenic groups. Bovine fibronectin (FNI) and gamma crystallin (CRYG) fragments were concordant with each other and with isocitrate dehydrogenase 1 (IDH1), representing the bovine syntenic group U17. The syntenic relationship of these genes is conserved on human chromosome 2q and also on mouse chromosome 1. In addition, bovine RFLPs were identified with both fibronectin and gamma crystallin probes. These polymorphisms will be used to study recombination between the syntenic loci in pedigreed herds and to mark a segment of the bovine genome that is likely homologous to the Lsh region of mouse chromosome 1, which confers resistance in mice to several intracellular parasites.

Parathyroid hormone and the beta hemoglobin gene cluster, which are closely linked on human chromosome 11p15, were localized to bovine syntenic group (U7) with the gene for catalase by the use of bovine x hamster hybrid somatic cells. Restriction fragment length polymorphisms (RFLPs) were followed through informative pedigrees to determine a linkage map distance of 15.6 +/- 5.4 cM between the parathyroid hormone and hemoglobin genes. Allelic frequencies of the DNA fragment were compared in a small sampling of cattle from five different breeds.

Recombination between Esterase-4 and Esterase-2 in the rat was not observed in 278 backcross offspring. Es-4 is thus included within the "esterase cluster" in Linkage group V. A new map of this region was constructed and the relationship of the four esterase loci was found to be: Es-4-(9.6+/-1.6 cM)-Es-2, Es-4-(1.5+/-0.7cM)-Es-3. Homology of this region with a region of Linkage Group XVIII (Chromosome 8) of the mouse was proposed on the basis of tissue distribution, subcellular localization and response of enzymes to inhibiotrs. Specifically, rat Es-1 was suggested as the homolog of mouse Es-6. An autosomal segment comprising at least 15cM of the rat and mouse genomes appears to have remained relatively intact with respect to genetic content during rodent speciation. In addition, a new polymorphism for mouse esterase was described. The locus was designated Esterase-10 (Es-10) and proposed as the mouse homolog of human Esterase D. Linkage of Es-10 with nucleoside phosphorylase-1-(Np-1) on Chromosome 14 was established.

The influence of interferon (IFN) on the natural resistance to Sendai virus was investigated in resistant (C57BL/6NCr) and susceptible (DBA/2NCr) mouse strains. After inoculation with strain 52 Sendai virus, the pulmonary titers of Sendai virus were similar in both mice strains, indicating that the quantity of virus in the lungs may not be a major factor in determination of resistance. The pulmonary IFN titers were higher in DBA/2 mice, indicating that increased susceptibility of DBA/2 mice is not a result of inadequate production of IFN. Treatment of both strains with exogenous IFN before and during viral infection induced an increased survival time in C57BL/6 mice, but eventual mortality was the same in both mouse strains. Administration of anti-IFN antibodies to both mouse strains during Sendai infection decreased mortality equally in both strains, compared with mortality in control mice. Seemingly, the difference in resistance to Sendai virus in DBA/2 and C57BL/6 mice was probably not a result of the beneficial effects of IFN. On the contrary, administration of anti-IFN antibodies decreased the susceptibility of both mouse strains.

Allelic differences at an esterase locus designated Es-6 exist between mouse strain C57 BL/6J and a laboratory stock of M.m. molossinus. Strain C57BL/6J has been assigned the allele Es-6a and M. m. molossinus the alternate allele Es-6b. Kidney expression of the electrophoretic esterase band controlled by the Es-6 locus is sex influenced, with increased activity apparently induced by testosterone. A four-point test cross established the gene order Os-Es-1-Es-6-Es-2 within a 10-cM segment on chromosome 8.

Somatic cell genetics coupled with enzyme electrophoresis has facilitated the mapping of PRGS and PAIS genes in cattle. Individual cow-hamster hybrid cell lines established by fusion of mutant CHO cells, ade-C and ade-G, with cattle leukocytes required complementing bovine genes for PRGS and PAIS, respectively, when propogated on selective media. Homogenates of 12 PRGS+ hybrid clones and 12 PAIS+ hybrid clones retained the bovine electromorph of SOD1 while extensively segregating 14 biochemical markers of other cattle syntenic groups. Secondary cattle-hamster hybrid subclones which segregated bovine PRGS and PAIS in late passages on nonselective media concordantly segregated bovine SOD1. These data support a syntenic relationship among PRGS, PAIS, and SOD1 on cattle syntenic group U10. An interferon receptor locus, IFREC, is also syntenic with SOD1. This synteny represents an extensive conservation of bovine U10 and the "Down syndrome region" of human chromosome 21.

A method for detecting two alleles at Np-1 (nucleoside phosphorylase) and three alleles at Es-10 (esterase 10) from mouse blood by cellulose acetate electrophoresis is described. The allelic constitution at these loci for 44 inbred strains and stocks was determined. The location of Np-1 on chromosome 14 was established by backcross experiments in which alleles at Np-1 and Robertsonian translocations were segregating. Es-10 was shown to be linked to Np-1, and the following genetic map of Chr 14 was constructed: centromere-(8.9 +/- 4.0 cM)-[Np-1, Wc]-(10.2 +/- 1.9 cM)-Es-10-(15.5 +/- 3.7 cM)-s. The homologous human loci, NP and ES-D, are not linked.

Cancers induced by physical or chemical carcinogens express tumor-specific antigens that are uniquely specific for any given tumor; therefore, there is a seemingly endless variety of these unique antigens. We have studied a UV-induced fibrosarcoma, designated 1591, to elucidate the obscure molecular nature and genetic origins of unique tumor-specific antigens. A monoclonal antibody raised against syngeneic 1591 tumor cells has unique tumor specificity. This tumor-specific monoclonal antibody precipitated from the tumor a 45-kDa molecule associated with a 12-kDa molecule having the pI of beta2-microglobulin. This and other evidence indicated that the 1591 tumor expresses a novel class I molecule. A 1591 variant selected for the absence of binding to the monoclonal antibody lacked the novel class I MHC molecule as well as reactivity with cytotoxic T lymphocytes specific for the 1591 tumor. Furthermore, tumor cells bearing the antigen are rejected while variants that have lost the antigen grow progressively. Fourteen of 14 host-selected progressor tumor variants lost reactivity with the monoclonal antibody and provided further evidence that this novel class I molecule is a transplantation antigen on the parental 1591 tumor required for immune rejection. The identification of a unique tumor-specific antigen as a novel class I major histocompatibility complex gene product allows us to search for the possible genetic mechanisms involved and to explore further the role such molecules play in tumor immunity and malignancy.

Malate dehydrogenase is present in most mammalian tissues in both supernatant and mitochondrial forms. Although genetic variation for the supernatant form has not been observed in the mouse, electrophoretic variants caused by alleles at the mitochondrial locus (Mor-1) have been previously described. We have located this locus 11.0 +/- 2.9 cM from the beta-glucuronidase structural gene, Gus, on chromosome 5. The gene order is Hm-Pgm-1-rd-bf-Gus-Mor-1. Thus Mor-1 is presently the most distal marker on chromosome 5. Three different nuclear loci for mitochondrial enzymes (Mod-2, Got-2, and Mor-1) have now been mapped in the mouse, all on different chromosomes.