Genetic variation and biochemical properties of esterase-18 (ES-18) in the laboratory rat (Rattus norvegicus): A new locus of esterase cluster 2 in linkage group V

A new liver-specific rat carboxylesterase isozyme (EC 3.1.1.1) designated esterase-18 (ES-18) is described. Genetic variation of ES-18 was examined in 93 inbred strains and substrains and a structural locusEs-18 was suggested, coding for either the presence (Es-18 ^a) or the absence (Es-18 ^b) of the isozyme. Linkage studies involving two backcross series revealed thatEs-18 resides in cluster 2 of LGV. No recombination betweenEs-18 and other cluster 2 loci was found in 19 lines of two RI strain sets or in the backcross series.R. K. was supported by the Sonderforschungsbereich 146 (Versuchstierforschung). O.D. was supported by the Deutsche Forschungsgemeinschaft (De 315/2). This is communication No. 65 of a research program devoted to the cellular distribution, regulation, and genetics of nonspecific esterases.     

Glutamate oxalate transaminase (GOT) genetics in Mus musculus: Linkage,polymorphism, and phenotypes of the Got-2 and Got-1 loci

A comparison of electrophoretic patterns of F₁ and backcross progeny of two inbred strains of mice has revealed a new autosomal variant of the mitochondrial form of GOT. The loci controlling the production of the soluble and mitochondrial forms of GOT have been designated Got-1 and Got-2, respectively. The two alleles of the Got-2 locus have been designated Got-2 ^a and Got-2 ^b, which represent the slow- and fast-migrating electrophoretic forms. Twenty-seven inbred strains of mice have been classified for Got-2 ^a and Got-2 ^b. It has been demonstrated that the polymorphism of Got-2 is widely distributed in feral mice. Got-2 was shown to be linked to Es-1, and evidence is also presented for linkage between Got-2 and Es-2, Es-5, and oligosyndactyly (Os). The absence of linkage of Got-2 to seven other loci has also been demonstrated. GOT was expressed in vitro in cell lines derived from human and mouse tissues.     

Esterase 13, a new mouse esterase locus with recessive expression and its genetic location on chromosome 9

A new esterase locus (Es-13) has been identified in Mus musculus. Strains AEJ/GnRk, LG/J, SJL/J, and SWR/J carry a recessive allele, Es-13 ^b, for a locus possibly involved in the posttranslational modification of a kidney esterase. All other strains observed carried the dominant Es-13 ^a 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 structural gene (Hdc-s) for mouse kidney histidine decarboxylase

The concentration of mouse kidney histidine decarboxylase (HDC) is modulated by estrogen, testosterone, and thyroxine in a tissue-specific manner. Variation in HDC levels between strains of mice can be used to investigate the genetic regulation of (i) enzyme structure, (ii) tissue specific expression, and (iii) induction and repression by hormones. Variation in the structure of HDC between different inbred strains of mice affecting its K _m for the cofactor pyridoxal-5-phosphate (PLP) and its heat stability has been discovered. The alternative phenotypes are additively inherited in crosses and the heat stability difference is due to alleles of a single structural gene, Hdc-s, which segregate among the BXD and BXH recombinant inbred strains. The allele Hdc-s ^b determines the heat-stable phenotype (C57BL substrains), and the allele Hdc-s ^d the heat-labile phenotype (DBA/2 and C3H/He strains). The alleles of the structural gene cosegregate with alleles of a regulatory gene previously named Hdc (determining kidney enzyme concentration); there were no recombinants among 38 RI strains. Therefore the two loci are less than 0.685 cM apart and comprise part of the HDC gene complex, [Hdc], on chromosome 2 of the mouse.This work was supported in part by an SERC studentship to S.A.M. and an MRC project grant to G.B.     

Esterase-30 (ES-30) of the house mouse: Biochemical characterization and genetics of a new carboxylesterase isozyme linked to cluster-2 loci on chromosome 8

A new carboxylesterase isozyme (EC 3.1.1.1), designated ES-30, is described in mouse liver. Two phenotypes were distinguished, ES-30A, a possible null type, was found in SPE/Pas and in other lines derived fromMus spretus, and ES-30B was found in BALB/cJ and other laboratory inbred strains. ES-30B is characterized by a distinct electrophoretic band when stained using 5-bromoindoxyl acetate as the substrate. After isolation and purification from other esterases by ion-exchange chromatography and molecular sieving, the molecular mass was estimated by two independent methods to be 62 and 64 kDa, respectively. The activity of ES-30B is higher in adult males than in females and can be stimulatedin vivo by testosterone. The distribution of phenotypes on the progeny of a backcross series suggests a separate locus,Es-30, with the allele a for absence andb for presence of the isozyme. LocusEs-30 is shown to be closely linked toEs-2 and toEs-7 of cluster-2 on chromosome 8. The gene orderEs-9—Got-2—(Es-2, Es-7, Es-30) is suggested. This work was supported by the Deutsche Forschungsgemeinschaft. This is communication No. 72 of a research program devoted to the cellular distribution, genetics, and regulation of nonspecific esterases.     

Es-6, a further polymorphic esterase in the rat

A further polymorphic rat esterase with broad tissue expression and restricted substrate specificity is described and tentatively called Es-6. Inbred rat strains have either fixed allele Es-6^F or fixed allele Es-6^S. Es-6 is not linked to the established esterase cluster consisting of the eight esterase loci Es-1, Es-2, Es-3M, Es-4M, Es-4W, Es-5 (=Es-3W), Es-7, and Es-8 in LG V of the rat or to RT1, Gc, c, a, and h. Esterases with apparently identical biochemical and genetical characteristics are Es-17 of the mouse and Es-A4 of humans.Supported by the Deutsche Forschungsgemeinschaft (Be 352/13 and Gu 105).     

Genetic Linkage between the AH Locus and a Major Gene That Inhibits Susceptibility to Audiogenic Seizures in Mice

Mice of the DBA/2 (D2) strain are highly susceptible to sound-induced seizures at 21 days of age; whereas, mice of the C57BL/6 (B6) strain are resistant to these seizures. Although the difference in susceptibility to audiogenic seizures (ASs) between these two strains is inherited as a multiple-factor trait, an association was observed between susceptibility to ASs and the Ah locus. The Ah locus controls the inducibility of aryl hydrocarbon hydroxylase (AHH) activity by a number of aromatic hydrocarbons. B6 mice carry the Ah^b allele and have inducible AHH activity; whereas, D2 mice carry the Ah^d allele and have noninducible activity. Inducibility is inherited as a Mendelian dominant trait in crosses between these strains. Mice carrying the Ah^b allele are generally less susceptible to ASs at 21 days of age than are mice carrying the Ah^d allele. The combined results from B6 x D2 recombinant inbred strains, congenic strains (where the Ah^b allele was placed into the D2 genome and the Ah^d allele placed into the B6 genome), the B6D2F₁ x D2 backcross generation, and a random survey of various inbred strains, suggest that the association between these two traits is due to genetic linkage, rather than to pleiotrophy or to chance. A major gene that inhibits susceptibility to ASs appears to be closely linked to the Ah locus. This gene has been designated Ias, for inhibition of ASs. A large portion of the genetic variability of AS susceptibility may be due to the segregation of Ias.     

The genetics of aryl hydrocarbon hydroxylase induction in mice: A single gene difference between C57BL/6J and DBA/2J

Twenty-one inbred strains of mice were surveyed for inducibility of hepatic aryl hydrocarbon hydroxylase (AHH) activity by the carcinogen 3-methylcholanthrene (MC). In 11 strains given MC, AHH activity increased 1.3- to 5-fold (inducible), whereas ten strains responded with a less than 0.5-fold increase (noninducible). Neither the inducible nor the noninducible class was homogeneous, and in each considerable variation was found in both the basal activity of AHH and the response to MC. Strains DBA/2J and C57BL/6J were chosen to represent the noninducible and inducible classes, respectively. In the crosses (C57BL/6 × DBA/2)F₁ × DBA/2 and (C57BL/6 × DBA/2)F₂, inducibility segregated as a single autosomal dominant gene. The gene symbols Ahh ⁱ and Ahh ⁿ are proposed for the alleles present in C57BL/6J and DBA/2J, respectively. No genetic linkage was found between the Ahh locus and the following loci: b, d, Es-1, Es-3, Gpd-1, Hbb, Id-1, Pgm-1, and sex. Some implications of this work in the study of mammalian enzyme induction and chemically induced carcinogenesis are discussed. There is a positive correlation between AHH inducibility and the development of an inflammatory response to the topical application of the carcinogen 7,12-dimethylbenzanthracene.     

Genetic control of two esterases of rat plasma (Rattus norvegicus)

Three electrophoretic variants of plasma esterase in the albumin zone, presumably carboxylesterase, have been demonstrated in 250 rats representing a laboratory population of Wistar rats. Electrophoretic variants of the enzyme are believed to be controlled by two codominant alleles at the autosomal locus referred to as Es-2. The variant of carboxylesterase represented by a fast-migrating single band on starch gel electrophoresis is determined by the gene named Es-2 ^a, whereas the slow-migrating variant, represented by two bands, is under control of the allelic gene Es-2 ^b. Animals with Es-2 ^a/Es-2 ^b genotype have three bands of carboxylesterase in the albumin zone. Genetically determined polymorphism of plasma esterase, presumably carboxylesterase, in the prealbumin zone was shown in both laboratory and wild populations of rats. Breeding tests suggest that the gene referred to as Es-1 ^a, responsible for the presence of carboxylesterase in the prealbumin zone, is inherited dominantly, whereas animals homozygous for the allele Es-1 ^b locked this esterase fraction.     

Biochemical genetics of Es-14 (formerly Es-Si) and a new esterase variation,Es-15, of the laboratory rat (Rattus norvegicus): Biochemistry,tissue expression,and linkage to Es-1 in linkage group V

The segregation of rat esterases controlled by loci residing in linkage group V (LGV) has been studied in two backcross series, (LEW/Han × BN/Han)F₁ × LEW/Han and (LEW/Han × LE/Han)F₁ × LEW/Han. Es-14 (formerly Es-Si) was shown to be closely linked to Es-1. A new esterase locus, Es-15, was described which codes for a liver isozyme. The distribution pattern of three alleles at the Es-15 locus is presented for 52 independent inbred strains. Close linkage of Es-15 to Es-14 and to Es-1 was established, proposing the following gene order: [Es-2, Es-10]—[ES-1, ES-14, ES-15]. The esterase loci on LGV are thus separated into two gene clusters, cluster 1 and cluster 2. These conclusions are supported by the strain distribution patterns of the two RI strain series, LXB and DXE.Otto von Deimling was supported by the Deutsche Forschungsgemeinschaft (De 315/2-1, communication No. 56).     

Esterase-16 (ES-16) of the rat (Rattus norvegicus): Identification and genetic characterization

Esterase-16, an esterase present in lung and other tissues of the laboratory rat, has been characterized by its biochemical properties (electrophoretic mobility, substrate pattern, sensitivity to inhibitors) and genetic variation in 107 inbred strains and substrains including 14 RI strains. It was classified as a carboxylesterase (EC 3.1.1.1). The phenotype ES-16A (BN/Han and 63 other strains) was defined as a narrow electrophoretic band migrating between ES-1A and ES-13A, ES-16B (LEW/Han and 42 other strains) exhibited the same electrophoretic mobility as ES-16A but was distinguished by its extremely weak activity. Segregation of ES-16 in RI strains and backcrosses indicated linkage to linkage group V (LGV). The Es-16 locus was tentatively placed into esterase cluster 2 and homology with Es-7 of the house mouse is proposed.     

Linkage analyses using biochemical variants in mice. II. Levulinate dehydratase and autosomal glucose 6-phosphate dehydrogenase

The level of hepatic -aminolevulinate dehydratase varies among inbred strains of mice and is regulated by codominant alleles at the Lv locus. Twenty-two inbred strains have been classified with respect to this locus. Lv is 5±2 recombination units from brown, b, in linkage group VIII. The locus for autosomal glucose 6-phosphate dehydrogenase (Gpd-1) has also been assigned to linkage group VIII and is 32±5 units from brown. The order of the loci is Lv-b-Gpd-1. Incidental note is made of linkage between the malic dehydrogenase (Mdh-1) and dilute (d) loci, linkage group II, with 10±3 % recombination between the two.Supported by the Roche Institute of Molecular Biology, Nutley, New Jersey, and by Public Health Service Research Grant CA-05873 from the National Cancer Institute.     

Gene responsible for dificient activity of the β subunit of C8, the eighth component of complement,is located on mouse chromosome 4

Sera from 73 strains of mice were tested for hemolytic activity through the classical and the alternative pathways (CP and AP) in a single radical hemolysis assay. Sera from 16 out of 45 laboratory inbred strains had n o lytic activity, and Ouchternoly analysis with anti-C5 serum showed them to be C5-deficient. Sera from 2 out of 28 strains derived from wild mice also had no lytic activity, but the C5 molecule was detectable in both. The hemolytic activity of sera from these strains can be restored serum deficient in C8-, leading us to conclude that strains M.MOL-MSM (MSM) and Mae are deficient in the subunit of C8. Typing of (DBA/2J ×MSM)F₁ hybrids and of progeny of a backcross to MSM showed that this C8 deficiency is controlled by a singles recessive gene, designated C8b; the allele with hemolytic activity is C8b ¹; and the allele with no activity C8b ⁰. Because of synteny homologies in mouse and human , we looked for and found close linkage between C8b and Pgm-2. Typing of recombinant mice for Mup-1 mapped the C8b locus 2.3 centimorgans (cM) telomeric to Pgm-2 on mouse chromosome 4.     

Glk: A locus controlling galactokinase activity in the mouse

Inbred strains of mice exhibit significant variation in whole blood galactokinase (GALK) activity. Activities tend to cluster into two classes, one class having approximately twice the activity of the other. Hybrids (F₁) between high and low strains have activity intermediate between the parental activities. Two sets of recombinant inbred (RI) lines were developed by brother-sister mating, beginning with F₂ generations of crosses between different pairs of high and low GALK activity strains. The RI lines segregated in terms of GALK activity, indicating single gene inheritance; this galactokinase locus has been designated Glk. The strain distribution patterns of both RI series agreed closely with esterase-3 (Es-3) alleles of the respective parental strains (31/34 independently derived strains were concordant for Es-3 and Glk genotypes), a finding consistent with a map distance between loci of 2.5 cM. Es-3 has been located on the distal end of chromosome 11. Glk, with its alleles Glk ^a (lower activity) and Glk ^b (higher activity), is therefore assigned to the same region.This project was supported by NIH Grants GM-02138 and GM-18684 from the National Institute of General Medical Sciences and HD-04861 and HD-00588 from the National Institute of Child Health and Human Development, and by a grant from the Clark Foundation, New York City. The Jackson Laboratory is fully certified by the American Association for Accreditation of Laboratory Animal Care.This work was carried out while J. D. M. was enrolled in the Summer Program for College, Graduate, and Medical Students at the Jackson Laboratory.     

Biochemical genetics of a new glucosephosphate isomerase allele (Gpi-1 c) from wild mice

We have found a new allele at the structural locus for glucosephosphate isomerase (called Gpi-1 ^c ) in a population of wild mice. The Gpi-1 ^c allele codes for an enzyme of greater cathodal electrophoretic mobility than either the Gpi-1 ^a or Gpi-1 ^b alleles found in the wild and in the SM/J and C57BL/6J inbred strains. Mice homozygous for Gpi-1 ^c have erythrocyte enzyme activity reduced to 33% of normal levels, altered pH profile, lowered heat stability, and normal K _m 's when compared with SM/J and C57BL/6J mice. The activity of the enzyme in brain, liver, and kidney is not so markedly lowered, although the electrophoretic mobility, pH profile, and heat stability are altered in these tissues. Deficiencies of erythrocyte glucosephosphate isomerase in man, to this level, can cause severe hemolytic anemia. Homozygotes for Gpi-1 ^c show only mild hematological symptoms. The frequency of Gpi-1 ^c in wild populations of mice is discussed and the occurrence of a further rare allele Gpi-1 ^d is reported.This work was supported by M.R.C. grants to Professor R. J. Berry and Dr. H. Kacser, whom we should also like to thank for much help and useful discussion.     

A genetic analysis of natural resistance to nonsyngeneic cells: The role of H-2

The genetic control of natural resistance in vivo to four natural killer (NK) cell-resistant H-2 homozygous lymphoid tumor cell lines was investigated by following the survival and organ distribution of cells prelabeled with radioactive iododeoxyuridine. Backcross mice derived from DBA/2J and CBA/J parents were injected with H-2 ^dtumor cells and tumor cell elimination was lowest in H-2 ^dhomozygotes. Natural killer cell activity was also reduced in mice with the H-2 ^dhaplotype, but no direct correlation between NK cell levels against YAC-1 or SL2-5 lymphoma cells and natural resistance in vivo was demonstrable. Analysis of 23 BXD recombinant inbred strains indicated that natural resistance to H-2 ^dtumors was restricted to H-2 ^bstrains. There was no direct association of NK cell activity with H-2 type in the BXD strains and NK cell levels did not correlate with tumor survival in vivo. By comparing natural resistance to H-2 ^dand H-2 ^btumors in DBA/2, C57BL/6, B6D2F₁, and B10.D2 mice we found that H-2 nonidentity between the tumor and the host, rather than the host H-2 haplotype, determined whether natural resistance occurred. Again, NK cell activity against YAC-1 cells was not predictive of tumor survival in these strains. These results provide genetic evidence that NK cells alone cannot account for natural resistance to H-2 nonidentical cells of hemopoietic origin.     

Mouse aldehyde dehydrogenase genetics: Positioning of Ahd-1 on chromosome 4

Electrophoretic variants of mitochondrial aldehyde dehydrogenase (AHD-A₂) are widely distributed among inbred strains of Mus musculus and have been used to localize the gene encoding AHD-A₂(Ahd-1) at the non-centromeric end of chromosome 4. In the mouse (Mus musculus), aldehyde dehydrogenase (AHD; E.C.1.2.1.3) exists as at least three isozymes which are differentially distributed in liver subcellular fractions (designated A₂, B₄ and Cy* for the mitochondrial, soluble and microsomal isozymes respectively) and in various tissues of this animal (Holmes, 1978a; 1978b; Timms & Holmes, 1981). Electrophoretic variants have been previously reported for the A₂ and B₄ isozymes among inbred strains of mice, and the genetic loci (designated Ahd-1 and Ahd-2) have been localized on chromosomes 4 and 19 respectively (Holmes, 1978b; Timms & Holmes, 1980). This paper describes further genetic analyses of AHD-A₂ enabling Ahd-1 to be positioned at the non-centromeric end of chromosome 4. Forty-three inbred strains of Mus musculus were used in these studies (Table 1). Two series of matings were carried out. 1) Female SM/J mice and male NZC/B1 mice were mated to obtain F, female offspring which were backcrossed to male NZC/B1 mice. These progeny were used to examine the segregation and linkage relationship of b (brown), Pgm-2 (encoding phosphoglucomutase B) and Ahd-1 (Table 2). 2) Female C57BL/6J mice and male SM/J. mice were mated to obtain F, female offspring which were backcrossed to male SM/J mice. The segregation and linkage relationship of Pgm-2, Gpd-1 (encoding the liver and kidney isozyme of hexose-6 phosphate dehydrogenase) and Ahd-1 were examined for these backcross progeny (Table 3). Methods for preparing liver and kidney extracts and the cellulose acetate electrophoresis procedure for typing Ahd-1, Pgm-2 and Gpd-1 have been previously described (Holmes, 1978b). A previous study has described the electrophoretic patterns for allelic variants for mitochondria1 AHD and of the hybrid phenotype for this enzyme (Holmes, 1978b). The three-allelic isozyme pattern for hybrid animals was consistent with a dimeric subunit structure: AHD-A¹A², AHD-A¹A² and AHD-3, with the A1 and A2 subunits being encoded by separate alleles at a single locus, designated Ahd-1 (Ahd-1^oand Ahd-1^brespectively). The distribution of these alleles among 43 inbred strains of mice is given in Table 1. The allelic variants were approximately equally distributed among the inbred strains examined and no divergence of phenotype was observed among the 6 substrains of C57BL mice (Ahd-1^aallele) and 5 substrains of BALB/c (Ahd-1^ballele) mice examined. Genetic variants for phosphoglucomutase-B (PGM-B) have been reported by Shows, Ruddle and Roderick (1969) and the gene (Pgm-2) was subsequently localized on chromosome 4 near b (brown) by Chapman, Ruddle and Roderick (1970). Table 2 illustrates the results of a three-point cross between b, Pgm-2 and Ahd-1. Variation from the expected 1:1:1:1:1:1 ratio for unlinked loci was significant(x²= 73.15; 7 df; P < 1 × 10^-5), indicating that the three loci are linked. Recombination frequency data are consistent with the gene order: b - Pgm-2 - Ahd-1 The second cross examined the segregation of Pgm-2, Ahd-1 and Gpd-1 loci (Table 3). The latter locus has been previously positioned on chromosome 4 (linkage group VIII) by Hutton & Roderick (1970) and Chapman (1975), and has been used to localize Ahd-1 in this region (Ahd-1 and Gpd-1 exhibit a recombination frequency of 10.3 ± 3.7 %) (Holmes, 1978b). The data from Table 3 is consistent with a gene order of Pgm-2 - Ahd-1 - Gpd-1. The recombination frequency data of Ahd-1 with Gpd-1, Pgm-2 and b also supports the proposal that Ahd-1 is localized between Pgm-2 and Gpd-1 (Tables 2 and 3; Holmes, 1978b). Recent metabolic studies have indicated that mitochondria1 aldehyde dehydrogenase (AHD) plays a very important role in the metabolism of acetaldehyde derived from ethanol, ensuring a low concentration of acetaldehyde in the blood leaving the liver (Grunnet, 1973; Parilla et al., 1974; Corral1 et al., 1976). Moreover, genetic variation of this isozyme in human livers has been recently reported (Harada et al., 1978), and this polymorphism has been proposed as the molecular basis for individual and racial differences in alcohol sensitivity (Goedde et al., 1979). Consequently, genetic analyses of mitochondria1 AHD are of particular significance to studies on the genetic control of alcohol metabolism in mammals. In summary, this report confirms previous studies which demonstrated that the genetic locus encoding mitochondrial aldehyde dehydrogenase in the mouse (Ahd-1) is on chromosome 4 (Holmes, 1978b), and positions the gene with respect to b (brown), Pgrn-2 (encoding phosphoglucomutase B) and Gpd-1 (encoding the liver and kidney isozyme of hexose-6-phosphate dehydrogenase). In addition, the distribution of the 2-allelic phenotypes for this isozyme has been examined among 43 in- bred strains of mice.     

Biochemical genetics of rat esterases: Polymorphism,tissue expression,and linkage of four loci

Two alleles at each of four esterase loci in Rattus norvegicus are described with regard to tissue expression, electrophoretic characterization, and genetic linkage. A previously described dominant gene for prealbumin serum esterase is demonstrated to exist as two codominant alleles in the genetically determined absence of the characteristic albumin esterase. The allelic composition of 16 inbred strains for four esterase genes is provided, and the heretofore ambiguous nomenclature of rat esterase genetics is standardized. Linkage of Es-1, Es-2, and Es-3 is demonstrated. Es-2 and Es-3 are tightly linked in that no recombination has been observed in 55 offspring. The same offspring demonstrated 9% recombination between Es-1 and the other two loci.This work was supported by a grant from the Brown-Hazen Fund of Research Corporation.     

Linkage of Pgm-3 in the house mouse and homologies of three phosphoglucomutase loci in mouse and man

The discovery of a third phosphoglucomutase locus (Pgm-3) in the house mouse is reported. Three alleles are recognized on the basis of differences in electrophoretic mobility and enzymatic activity. Pgm-3 ^a (fast mobility and high activity) is present in inbred strain C57BL/10J and 24 other strains; Pgm-3 ^b (slow mobility and high activity) is present in LP/Pas and six other strains; and Pgm-3 ^c (no detectable activity in any tissue tested) is present in strain DBA/2J and 14 other strains. Seventy-four recombinant inbred strains derived from progenitors that differed at Pgm-3 were used to study genic linkage. Pgm-3 is on chromosome 9 and is linked to Sep-1, d, Mod-1, and Ltw-3. Gene order and recombination frequencies are estimated as d 3.8±1.8% Pgm-3 2.3±1.2% Mod-1. Substrate specificities and cofactor requirements show that mouse Pgm-1 is homologous with human Pgm-2, mouse Pgm-2 with human Pgm-1, and mouse Pgm-3 with human Pgm-3.This research was supported in part by NIH Research Grant GM18684 from the National Institute of General Medical Sciences to B.A.T. and by grants from NIH A105531-02 and the Volkswagon Foundation to Jan Klein. J.H.N. was a recipient of a Fellowship from the Max-Planck-Gesellschaft, Munich. G.S. and J.K. were supported by funds from the Deutsche Forschungsgemeinschaft.     

Peptidase-3 (Pep-3), dipeptidase variant in the rat homologous to mouse Pep-3 (Dip-1) and human PEP-C

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-3 ^a and is characteristic of strain ACI/Pit. A faster (more anodal) electrophoretic mobility is the product of the Pep-3 ^b allele in strain F344/Pit. Twenty-five additional inbred strains carry Pep-3 ^a and 16 others carry Pep-3 ^b . 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).