Kidney esterases of Mus musculus: Further polymorphism of esterase-6, esterase-9, and a new esterase,esterase-20

The comparison of results obtained by different separation and staining techniques permits the definition of esterase-6 in comparison with esterase-9 and a new esterase, esterase-20. Alleles of Es-6 affect the product's ability to aggregate. Esterase-20 may be an aggregated product of Es-9. The close linkage of Es-6 and Es-9 is confirmed. Homology of esterase-6 with esterases from other mammalian species is also suggested.HRN was supported by the Medical Research Council. This is communication No. 32 of a research program devoted to the cellular distribution, genetics, and regulation of nonspecific esterases.     

Polymorphism of esterase-10 in Mus musculus

An esterase, esterase-10, in the house mouse, Mus musculus, is specific for esters of 4-methylumbelliferone and exhibits a polymorphism detectable by electrophoresis. Fifteen inbred strains and two outbred strains have been examined for this polymorphism, and two phenotypes, ES-10A and ES-10B, have been observed. Each phenotype manifests itself as a single band of enzyme activity, but under the electrophoretic conditions used the ES-10A phenotype has less anodal electrophoretic mobility than the ES-10B phenotype. In F₁ hybrids (C3H/He/Lac×C57BL/Gr) a third phenotype was observed, ES-10AB, consisting of three bands of enzyme activity, two of which correspond to the parental forms and the third with intermediate mobility. The triple-band pattern in the F₁ hybrids indicates that esterase-10 is a dimeric enzyme protein.This work was supported by the Medical Research Council.     

Linkage of the locus for conversion of albumin (Acf-1)in the house mouse,Mus musculus

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.This work was supported by NIH Postdoctoral Fellowship 1F32 GM0527701, Grant BMS75-03397 from the National Science Foundation, Grant ACS VC-17-R from the American Cancer Society, and Contract NO1-ES42159 from the National Institute of Environmental Health Sciences. The Jackson Laboratory is fully accredited by the American Association for the Accreditation of Laboratory Animal Care.     

Genetic analysis of protein variations in Mus musculus using two-dimensional electrophoresis

We have investigated the variation of proteins from crude homogenates of mouse kidneys in several strains of Mus musculus by means of two-dimensional electrophoresis. In this study, we have used the strains C57BL/6J, DBA/2J, CD-1, M. m. castaneus, and M. m. molossinus, as well as offspring from crosses among these strains. Out of the 100 loci screened, we have found nine loci showing interstrain differences. We have been able to identify three proteins as Id-1, Car-2, and Sep-1. The remaining variants are probably new loci in the mouse. Most of the variants (seven) can be mapped to a chromosome. We have found also that differences in the protein pattern as seen on two-dimensional gels are small among subspecies of Mus musculus.     

Nonspecific esterases of Mus musculus

Seventeen genes controlling the expression of carboxylic ester hydrolases, commonly known as esterases, have been identified in the mouse Mus musculus. Seven esterase loci are found on chromosome 8, where two clusters of esterase loci occur. It seems probable that the genes within these clusters have arisen from a common ancestral gene by tandem duplication. Close linkage of esterase genes is also found in the rat, rabbit, and prairie vole. Some mouse esterases appear to be homologous with certain human esterases. The function of these nonspecific enzymes is still unknown.     

Xylose dehydrogenase-1, a new gene on mouse chromosome 7

We report a new enzyme xylose dehydrogenase, the structural locus for which is on chromosome 7 of the mouse, closely linked to Tam-1. Three alleles have been detected in both laboratory strains and wild populations. Two of these determine proteins differing in electrophoretic mobility and the third is a null. This easily scored variation may prove useful both for gene mapping and in population genetics.This work was supported by the Medical Research Council.     

Esterases of Mus musculus: Substrate and inhibition characteristics,new isozymes,and homologies with man

A wide range of fluorogenic and naphthol esters has been tested as substrates for mouse esterases. New esterases have been identified in liver and kidney extracts with palmityl, oleyl, and elaidyl esters. From substrate, inhibition, and molecular weight studies, three homologies between human and mouse esterases are suggested. A new allele at Es-6 is also described.This work was supported by the Medical Research Council.     

Genetics of alkaline phosphatase of the small intestine of the house mouse (Mus musculus)

Four inbred strains of mice exhibited either slow (PL/J), intermediate (DBA/2J, LP/J), or fast (SWR/J) rates of migration of duodenal alkaline phosphatase on cellulose acetate electrophoresis. Hybrids of these strains also had intermediate rates of migration regardless of the combination of strains used as parents. Strain differences were present in all regions of the small but not the large intestine. Crosses of the PL/J strain to hybrids between this strain and the other three strains gave a 1:1 segregation of the slow and intermediate patterns. The symbol Akp-3 is proposed for the locus responsible for the slower migration of the enzyme in this strain. Data from the LP/J × PL/J hybrid crossed with the PL/J strain showed linkage with two loci on chromosome 1 as follows: centromere—Idh-1–13.8±3.1 cM—Akp-3–8.9±2.6 cM—Pep-3. The available data do not reveal the genetic basis for the faster migration rate of the enzyme from the SWR/J strain, but a different response to neuraminidase and apparent nonlinkage to the Pep-3 locus suggest that a locus other than Akp-3 is responsible.This work was supported by a grant from the University Research Committee, Indiana State University.     

Polymorphism of kidney pyruvate kinase in the mouse is determined by a gene,Pk-3, on chromosome 9

An electrophoretically detectable variant of pyruvate kinase (EC 2.7.1.40) has been found in the house mouse Mus musculus. The variant was seen in all tissues examined except liver and red cells. The gene (Pk-3) determining this electrophoretic variation is inherited as an autosomal codominant located on chromosome 9. Our data confirm that the genetic determination of pyruvate kinase in liver and red cells is separate from that in other tissues. In addition, our results indicate that the muscle (M₁) and kidney (M₂) pyruvate kinase isozymes share at least one genetic determinant and may in fact be determined by the same structural gene.This work was supported by the Medical Research Council and by NIH Grants GM 20919 and RR 01183. The Jackson Laboratory is fully accredited by the American Association for Accreditation of Laboratory Animal Care.     

Structural differences between albumin A and albumin C of the house mouse,Mus musculus

Two albumins, albumin A from C3H mice and albumin C isolated from descendents of the wild mice in which the variant was first uncovered, were found to differ in their electrophoretic properties. Albumin C was shown to bind two more H⁺ ions than albumin A at pH 5.4. Peptide mapping after trypsin digestion revealed that albumin C had three peptides (TP-C1, TP-C2, and TP-C3) which were missing in albumin A. The latter likewise had a peptide (TP-A1) which was not found in albumin C. An amino acid analysis of the variant peptides suggests that TP-A1 had been split into TP-C1 and TP-C2 on digestion with trypsin, because a glutamic acid in TP-A1 was replaced by a lysine. This change would also appropriately alter the electrophoretic properties of albumin C. No obvious counterpart was discovered for TP-C3 of albumin C in albumin A.This work was supported by a grant from the National Research Council of Canada.     

Esr,a second locus in the house mouse controlling esterase-5

Electrophoretic variation characterized by the presence (ES-5B⁺) or absence (ES-5B^–) of esterase-5B in the plasma of the house mouse has been observed. It is suggested that the expression of esterase-5B is controlled by an autosomal locus, Esr, linked to Ldr-1 on chromosome 6, in addition to the presumptive structural locus Es-5, which is located on chromosome 8. A gene order of Lyt-3-Esr-Ldr-1 was determined by two crosses.Supported by the Deutsche Forschungsgemeinschaft (SFB 46).This is communication No. 33 of a research program devoted to the investigation of cellular distribution and genetics of nonspecific esterases.     

Genetic variation for prolidase (PEP-4) in the mouse maps near the gene for glucosephosphate isomerase (GPI-1) on chromosome 7

An inherited electrophoretic variant of prolidase (EC 3.4.13.9), also called peptidase 4 (PEP-4), has been discovered among inbred strains of mice. Analysis of progeny from reciprocal backcrosses established that the electrophoretic forms are expressed codominantly and that Pep-4 is located between the genes for glucosephosphate isomerase (Gpi-1) and pink-eyed dilution (p) on chromosome 7. These data define a region of conserved gene linkage between mouse chromosome 7 and human chromosome 19, as originally indicated by somatic cell hybrid studies, and imply that human prolidase (PEPD) is located in the region of human chromosome 19 pter q13.Research sponsored by the Office of Health and Environmental Research, U.S. Department of Energy, under Contract W-7405-eng-26 with the Union Carbide Corporation.By acceptance of this article, the publisher or recipient acknowledges the right of the U.S. Government to retain a nonexclusive, royalty-free license in and to any copyright covering the article.     

Allozymic Polymorphism Among 14 Populations of the House Mouse, Mus musculus domesticus, From Greece

Nineteen loci from 239 individuals of the house mouse Mus musculus domesticus (Rodentia, Muridae) were analyzed by means of thin layer electrophoresis. The mice were collected from 14 localities of Greece mainly confined to the area of NW Peloponnese, where a Robertsonian (Rb) system is observed. The individuals were chromosomally characterized by nine diploid numbers, the 2n = 24, 26, 27, 28, 29, 30, 31, 32, and 40. The statistic elaboration revealed that all 14 populations studied were not characterized by cohesive demic structure and high inbreed levels while the gene flow among them has resulted in low levels of genetic differentiation. The resulting values for Neis genetic distance corresponded to distances known for the level of geographical populations of, M. musculus. Wagners cladogram for the phylogenetic relations between the populations studied implied that it is the diploid number, rather than the geographical factor, that characterizes or dominates each population, which mainly influences the phylogenetic relationships.     

Linkage relationships of peptidase-7, Pep-7, in the mouse

An electrophoretically detectable variant of peptidase-7 in Mus musculus has been found and used to locate the structural gene, Pep-7, on chromosome 5. Gene order and recombination frequencies are estimated as Pep-7 3.5±2.0 Rw 8.8±2.2 go 20.0±4.6 bf.     

The aryl hydrocarbon hydroxylase (Ah) locus and a novel restriction-fragment length polymorphism (RFLP) are located on mouse chromosome 12

The aryl hydrocarbon hydroxylase (Ah) locus that controls the induction of chemical carcinogen-metabolizing enzymes in mice has been found to be linked to a new restriction-fragment length polymorphism (RFLP). Only C57 BL/6 and closely related inbred strains displayed a 7.6-kbHindIII restriction fragment, while all other inbred strains tested displayed an 11.2-kbHindIII restriction fragment when using plasmid pRC2.3 as the hybridization probe. Polymorphisms in this region can also be detected with two other restriction enzymes:SacI andEcoRV. Linkage ofAh and the restriction-fragment length polymorphism was first detected using the BXD (C57BL/6 × DBA/2) recombinant inbred strains and was confirmed by a backcross. Both the restriction-fragment length polymorphism andAh were not linked to the standard genetic markersHba, Hbb, b, d, C-3, andW. However, comparison of the RFLP strain distribution pattern in the BXD recombinant inbred set with the strain distribution pattern of another RFLP, known to be located on chromosome 12, shows complete concordance in 24 of 24 strains, thereby locatingAh on chromosome 12.This research was funded in part by National Institutes of Health Grant AM31104 and by BRSG S-07RR05365-23 to J.B.W. This is contribution number 0869 from the Department of Cell and Molecular Biology.     

Svp-3, a third polymorphic locus for mouse seminal vesicle proteins

The B10.AKM/Sn congenic strain displays a particular phenotype of mouse seminal vesicle proteins representing the third polymorphic locus of this system. The Svp-3 symbol was assigned to this locus with two codominant alleles, Svp-3a found in the B10.AKM/Sn strain and Svp-3b expressed by all the other strains so far tested. The Svp-3 locus appears tightly linked to Svp-1 on chromosome 2.     

Prt-4 and Prt-5: New constituents of a gene cluster on chromosome 7 coding for esterproteases in the submandibular gland of the house mouse (Mus musculus)

The heredity and linkage of gene loci were established for two different enzymes with esterproteolytic activity from mouse submandibular gland: protease A and protease E. Based upon strain distribution and biochemical properties of the two esterproteases, the existence of two corresponding structural loci is proposed: Prt-4 (protease A) and Prt-5 (protease E). Prt-4 and Prt-5 proved to be different from Tam-1. From a four-point-cross, the gene order Gpi-1-(Tam-1, Prt-4, Prt-5)-c is suggested. Thus a gene cluster was shown to exist on chromosome 7 coding for esterproteases, all of which are controlled by testosterone.This work was supported by grants from the Deutsche Forschungsgemeinschaft, Bonn (SFB 46).     

Genomic copy number variation in Mus musculus

Background

Copy number variation is an important dimension of genetic diversity and has implications in development and disease. As an important model organism, the mouse is a prime candidate for copy number variant (CNV) characterization, but this has yet to be completed for a large sample size. Here we report CNV analysis of publicly available, high-density microarray data files for 351 mouse tail samples, including 290 mice that had not been characterized for CNVs previously.

Results

We found 9634 putative autosomal CNVs across the samples affecting 6.87 % of the mouse reference genome. We find significant differences in the degree of CNV uniqueness (single sample occurrence) and the nature of CNV-gene overlap between wild-caught mice and classical laboratory strains. CNV-gene overlap was associated with lipid metabolism, pheromone response and olfaction compared to immunity, carbohydrate metabolism and amino-acid metabolism for wild-caught mice and classical laboratory strains, respectively. Using two subspecies of wild-caught Mus musculus, we identified putative CNVs unique to those subspecies and show this diversity is better captured by wild-derived laboratory strains than by the classical laboratory strains. A total of 9 genic copy number variable regions (CNVRs) were selected for experimental confirmation by droplet digital PCR (ddPCR).

Conclusion

The analysis we present is a comprehensive, genome-wide analysis of CNVs in Mus musculus, which increases the number of known variants in the species and will accelerate the identification of novel variants in future studies.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1713-z) contains supplementary material, which is available to authorized users.     

Esterase-8 (Es-8): Characterization,polymorphism, and linkage of an erythrocyte esterase locus on chromosome 7 of Mus musculus

An electrophoretic polymorphism of an erythrocyte esterase, esterase-8, specific for the substrates α- and β-naphthyl acetate has been observed in the Asian house mouse, Mus musculus castaneus. M. m. castaneus is interfertile with inbred strains of mice, and F₁ hybrids (C57BL/6J × castaneus)F₁ and (SWR/J × castaneus)F₁ show a double-banded phenotype similar to a mixture of parental forms. This pattern suggests codominant expression of a structural gene difference. In backcrosses, ES-8 segregated as a single autosomal gene, designated Es-8, linked to Gpi-1 on chromosome 7. A gene order of Es-8, Gpi-1, c, Mod-2, and Hbb was determined from a series of crosses.