Protein-charge mutations in mice.
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Animals↗
Biomedical subjects
W Pretsch
Publications and source records attributed to W Pretsch.
An inherited variant of mouse sn-glycerol-3-phosphate dehydrogenase detected by isoelectric focusing: genetical and biochemical analyses.
An electrophoretically detectable mutant of sn-glycerol-3-phosphate dehydrogenase (GPDH) has been found in the offspring of 1-ethyl-1-nitrosourea-treated mice. The banding alteration was detected by isoelectric focusing (IEF) of crude liver extract on polyacrylamide gels. The GPDH alteration is not organ specific. The mutant protein is more positively charged than the wild type. The mutation is codominantly expressed. Heterozygous and homozygous mutants have distinguishable IEF banding patterns. The specific activity of GPDH is not altered by the mutation. The mutated allele causes a greater heat stability to the GPDH protein. Enzymes extracted from the three genotypes are indistinguishable in terms of their pH optima. Gdc-1e is proposed as the allele symbol for the new mutation.
Alleles↗
A new pyruvate kinase mutation with hyperactivity in the mouse.
A mouse mutant with pyruvate kinase (PK) hyperactivity has been found in offspring of 1-ethyl-1-nitrosourea (ENU)-treated male mice. The activity alteration was detected in the blood and could also be found in the liver but not in the muscle, kidney, heart, spleen, lung, or brain. Heterozygous mice have erythrocyte PK activity enhanced up to about 160% and homozygotes up to about 240%, compared to homozygous wild types. The mutation is codominantly expressed. The heterozygous and homozygous mutants are viable and fully fertile and do not show symptoms of erythrocytosis. The mutation does not affect the heat stability, the electrophoretic mobility, or the Km (for phosphoenolpyruvate) of the PK molecule. It is suggested that the regulatory locus of PK-1 is affected by this mutation. The observations support also the theory of one structural locus for the erythrocyte and liver isozymes.
Animals↗
Detection of dominant enzyme mutants in mice: model studies for mutations in man.
After intraperitoneal injection with the mutagens procarbazine hydrochloride (PHCl) or N-ethyl-N-nitrosourea (ENU), male (101/EL X C3H/EL)F1 mice were mated with untreated test-stock females. The offspring were screened for induced mutations that cause alterations of two different enzyme properties. Charge modifications were analysed by separation of liver enzymes by isoelectric focussing on polyacrylamide gels. Banding patterns of six enzyme systems were checked by using the agar contact replica technique and specific activity stainings. No mutant was found in 5278 offspring of the control group. After paternal treatment of spermatogonia, the mutant frequency was one mutant in 5630 offspring (600 mg PHCl per kg body weight), one mutant in 1892 offspring (160 mg/kg ENU), two mutants and two presumed mutants, which died before genetic confirmation, in 4136 offspring (250 mg/kg ENU). No mutant was detected with PHCl and the two ENU doses in the postspermatogonial treatment groups of 469, 1088, and 2020 offspring, respectively. Specific activities of 10 erythrocyte enzymes were measured in the blood with an automatic enzyme analyser. To date, in the spermatogonial treatment group, findings have been: no mutant in 3610 controls, seven mutants in 3509 offspring (80 mg/kg ENU), five mutants in 800 offspring (160 mg/kg ENU) and four mutants in 759 offspring (250 mg/kg ENU). Of these 16 independent mutants, 10 caused reduced enzyme activity and six increased it.
Animals↗
A mutation affecting the lactate dehydrogenase locus Ldh-1 in the mouse-I. Genetical and electrophoretical characterization.
(101/El x C3H/el)F1 male mice were infected intraperitoneally with the mutagen procarbazine hydrochloride and immediately caged with untreated test-stock females. Crude liver extracts from the offspring were subjected to polyacrylamide gel isoelectric focusing, and the gels were stained for six enzymes. In the experimental group (mutagen treated spermatogonial germ-cell stage), a dominant inherited banding alteration of the lactate dehydrogenase (LDH) pattern was detected. By crossing the heterozygous mutants, homozygotes were obtained that showed much less gel staining intensity. The mutation is codominantly expressed with 100% penetrance. The banding alteration was also observed in muscle, kidney, heart, blood, brain, testis, spleen, and lung. Polyacrylamide gel electrophoresis was performed with all the tissues examined. The mutation causes the intensity of the band corresponding to LDH-A (primary molecular form in muscle) to decrease from that of the wild type, while the intensity of the bands corresponding to LDH-B (primary molecular form in heart) remains constant. It is concluded that the mutation affects the locus coding for LDH of the muscle type. Ldh-1c is proposed as the allele symbol.
Animals↗
Induction of gene mutations in mice: the multiple endpoint approach.
The multiple endpoint mammalian mutagenesis approach developed in our institute screens in the same animal for recessive specific-locus alleles at 7 loci, approximately 30 loci coding for dominant-cataract mutations, 23 loci controlling protein-charge changes and 12 loci for enzyme-activity alterations. Experiments to screen for the approximately 70 loci in the same offspring of treated male mice were performed with ethylnitrosourea (ENU), procarbazine and X-ray exposure. Mutations were recovered for each genetic endpoint in all treatment groups where a sufficient number of offspring was scored. ENU treatment is highly effective in inducing mutations to all genetic endpoints. The mutations were confirmed by breeding tests. The mutation rates to specific-locus and enzyme-activity alleles were both higher than the mutation rates to either dominant-cataract or protein-charge alleles. The advantages and possibilities of the multiple endpoint approach are discussed in detail.
Animals↗
Genetic localization and phenotypic expression of X-linked cataract (Xcat) in Mus musculus.
Linkage data relative to the markers tabby and glucose-6-phosphate dehydrogenase are presented to locate X-linked cataract (Xcat) in the distal portion of the mouse X-chromosome between jimpy and hypophosphatemia. The human X-linked cataract-dental syndrome, Nance-Horan Syndrome, also maps closely to human hypophosphatemia and would suggest homology between mouse Xcat and human Nance-Horan Syndrome genes. In hemizygous males and homozygous females penetrance is complete with only slight variation in the degree of expression. Phenotypic expression in Xcat heterozygous females ranges from totally clear to totally opaque lenses. The phenotypic expression between the two lenses of a heterozygous individual could also vary between totally clear and totally opaque lenses. However, a correlation in the degree of expression between the eyes of an individual was observed. A variegated pattern of lens opacity was evident in female heterozygotes. Based on these observations, the site of gene action for the Xcat locus is suggested to be endogenous to the lens cells and the precursor cell population of the lens is concluded to be small. The identification of an X-linked cataract locus is an important contribution to the estimate of the number of mutable loci resulting in cataract, an estimate required so that dominant cataract mutagenesis results may be expressed on a per locus basis. The Xcat mutation may be a useful marker for a distal region of the mouse X-chromosome which is relatively sparsely marked and the X-linked cataract mutation may be employed in gene expression and lens development studies.
Animals↗