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M H Meisler

Publications and source records attributed to M H Meisler.

123 records · Page 7Linked to original sources
PubMed1980

Rate of spontaneous mutation at human loci encoding protein structure.

The techniques of electrophoresis were used in a search for evidence of mutation affecting protein structure, the indicators being hemoglobin and a set of serum proteins and erythrocyte enzymes. Among 94,796 locus tests on Amerindians from Central and South America, there was no evidence for mutation. Among 105,649 locus tests on newborn infants in Ann Arbor, Michigan, there was also no evidence for mutation. We have previously failed to encounter any mutations in a series of 208,196 locus tests involving Japanese children [Neel, J. V., Satoh, C., Hamilton, H. B., Otake, M., Goriki, K., Kageoka, T., Fugita, M., Neriishi, S & Asakawa,J. (1980) Proc. Natl. Acad. Sci. USA 77, 4221-4225], and H. Harris, D. A. Hopkinson, and E. B. Robson [(1974) Ann. Hum. Genet. 37, 237-253] found no mutations in 113,478 locus tests on inhabitants of the United Kingdom. This failure to demonstrate any mutations of this type in a total of 522,119 locus tests excludes, at the 95% level of probability, a mutation rate greater than 0.6 X 10(-5)/locus per generation in this combination of populations.

Blood Proteins↗
PubMed1980

Rare structural variants of human and murine uroporphyrinogen I synthase.

An isoelectric focusing method for detection of structural variants of the enzyme uroporphyrinogen I synthase [porphobilinogen ammonia-lyase (polymerizing), EC 4.3.1.8] in mammalian tissues has been developed. Mouse and human erythrocytes contain one or two major isozymes of uroporphyrinogen I synthase, respectively. Other tissues contain a set of more acidic isozymes that are encoded by the same structural gene as the erythrocyte isozymes. Mouse populations studied with this method were monomorphic for uroporphyrinogen I synthase, with the exception of one feral mouse population. The pedigree of a human family with a rare structural variant is consistent with autosomal linkage of the structural gene. This system provides a convenient isozyme marker for genetic studies and will facilitate determination of the chromosomal location of the uroporphyrinogen I synthase locus.

Ammonia-Lyases↗
PubMed1979

A sensitive fluorescent assay for N-acetyltransferase activity in human lymphocytes from newborns and adults.

We have developed a simplified assay for the enzyme N-acetyltransferase, based upon the loss of fluorescence after acetylation of the substrate p-aminobenzoic acid. This method is sufficiently sensitive to permit the quantitation of N-acetyltransferase activity in 10(5) human lymphocytes. Using this method, we have compared the level of N-acetyltransferase activity in lymphocytes from adult peripheral blood and from cord blood samples.

Acetyltransferases↗
PubMed1979

GM1-gangliosidosis: chromosome 3 assignment of the beta-galactosidase-A gene (beta GALA).

The structural gene (beta GALA) coding for lysosomal beta-galactosidase-A (EC 3.2.1.23) has been assigned to human chromosome 3 using man--mouse somatic cell hybrids. Human beta-galactosidase-A was identified in cell hybrids with a species-specific antiserum to human liver beta-galactosidase-A. The antiserum precipitates beta-galactosidase-A from human tissues, cultured cells, and cell hybrids, and recognizes cross-reacting material from a patient with GM1 gangliosidosis. We have analyzed 90 primary man--mouse hybrids derived from 12 separate fusion experiments utilizing cells from 9 individuals. Enzyme segregation analysis excluded all chromosomes for beta GALA assignment except chromosome 3. Concordant segregation of chromosomes and enzymes in 16 cell hybrids demonstrated assignment of beta GALA to chromosome 3; all other chromosomes were excluded. The evidence suggests that GM1 gangliosidosis is a consequence of mutation at this beta GALA locus on chromosome 3.

Animals↗
PubMed1978

Synthesis and secretion of kidney beta-galactosidase in mutant le/le mice.

We have found that the pigmentation mutant light ear in the mouse has a striking effect on lysosomes in the kidney. Male mice homozygous for the le mutant allele have a 4-fold elevated concentration of kidney beta-galactosidase (EC 3.2.1.23). The abnormal elevation of kidney beta-galactosidase is the net result of two processes. First, beta-galactosidase is elevated due to the defective urinary secretion of lysosomal enzymes which is a specific effect of the le mutation. Secondly, this effect is most evident in males and testosterone-treated females because of the induction of beta-galactosidase synthesis by testosterone, which occurs in +/+ as well as in mutant mice. The pale-ear mutation (ep) which mimics the pigmentation phenotype of le also has a similar effect on kidney lysosomes.

Aging↗
PubMed1976

Effects of the Bgs locus on mouse beta-galactosidase.

The Bgs locus determines tissue levels of beta-galactosidase in the mouse, so that enzyme levels are twice as high in mice carrying the Bgsh allele as in mice carrying the Bgsd allele (Felton et al., 1974). By immunotitration with antiserum to purified beta-galactosidase, we have found that the Bgs locus influences the amount of enzyme protein present in the tissues. We have utilized recombinant inbred lines derived from a cross between C57BL/6J and DBA/2J mice to confirm the location of the Bgs locus on chromosome 9. The inhibition of mouse beta-galactosidase by the active-site-directed reagent N-bromoacetyl-beta-D-galactosylamine has been investigated. beta-Galactosidase from the high and low Bgs strains has identical affinity for this inhibitor.

Acetylgalactosamine↗
PubMed1975

Inhibition of human liver beta-galactosidases and beta-glucosidase by n-bromoacetyl-beta-D-galactosylamine.

N-Bromoacetyl-beta-D-galactosylamine is an irreversible inhibitor of the 'acid' and the 'neutral' beta-galactosidases (beta-D-galactoside galactohydrolase, EC 3.2.1.23) of human liver. The inactivation of acid beta-galactosidase appears to involve a group with a pKa = 4.5. The inhibition of neutral beta-galactosidase only occurs above pH 8.0. Both enzymes are protected against inhibition by the presence of substrates, suggesting that the inhibitor reacts with the active site of the enzymes. Other lysosomal hydrolases are not inhibited by N-bromoacetyl-beta-D-galactosylamine, with the exception of 'neutral' beta-glucosidase (beta-D-glucoside glucohydrolase, EC 3.2.1.21). The pH dependence of neutral beta-glucosidase inactivation is essentially identical to that of the neutral beta-galactosidase. Inhibition of beta-glucosidase by this galactose derivative suggests that the same enzyme may bind glucosides and galactosides. Furthermore, both neutral beta-galactosidase and beta-glucosidase are inactivated at 52 degrees C with a half-life of 7.5 min. The presence of a single enzyme with both beta-glucosidase and beta-galactosidase activities is also supported by mixed-substrate experiments.

Acetylgalactosamine↗
PubMed1966

Nucleohistone dissociation by ganglioside micelles.

The sialic acid-containing glycosphingolipids known as gangliosides can reverse the heat stabilization of DNA by histones. The ability of pure mono-and disialogangliosides to dissociate reconstituted nucleohistone is directly dependent on their sialic acid content; they are effective in concenitrations above their critical micelle concentration.

Animals↗
PubMedDate not supplied

Additional evidence for the close linkage of amy-1 and amy-2 in the mouse.

The enzyme amylase is produced in large quantities in two mammalian tissues, the pancreas and the parotid salivary gland. A substantial body of biochemical and genetic evidence is consistent with the existence of distinct genes encoding salivary and pancreatic amylases, but testcrosses in mice have indicated that the two putative loci must be very closely linked. We have studied crosses between two pairs of inbred mice that differ with respect to electrophoretic mobility of salivary and pancreatic amylases. Among 343 potentially recombinant chromosomes examined, no recombinants were found. Our data sets an upper limit of 0.87 cM (P = 0.95) for the distance between the salivary and pancreatic loci.

Amylases↗
PubMedDate not supplied

Pigmentation and lysosomal phenotypes in mice doubly homozygous for both light-ear and pale-ear mutant alleles.

We have developed a new strain of mice homozygous for mutant alleles at both the light-ear locus on chromosome 5 and the pale-ear locus on chromosome 19. The pigmentation pattern of the double mutants, designated light-pale, is indistinguishable from the parental type. Elevated concentrations of lysosomal enzymes observed in certain tissues of the light-ear and pale-ear singly homozygous mice also are present in the double mutants, and are quantitatively indistinguishable from either parent. Although both mutations have pleiotropic effects on organelles in several tissues, neither locus influences the secretion of pancreatic zymogen granules. The close similarity in phenotypes of light ear, pale ear, and light-pale mice suggest that the le and ep loci encode different subunits of a multimeric protein, and that mutations affecting either subunit result in comparable losses of function.

Alleles↗
PubMedDate not supplied

Optic, olfactory, and vestibular dysmorphogenesis in the homozygous mouse insertional mutant Tg9257.

The transgene insertional mutation 9257 on mouse chromosome 18 was originally identified by the circling behavior caused by vestibular abnormalities in heterozygous mutants. To characterize the homozygous phenotype, we generated F2 offspring from the cross (C57BL/6J-tg/+ x DBA/2J). Eye defects ranging in severity from microphthalmia to anophthalmia were observed in the tg/tg offspring. Dysmorphic development of the lens was evident as early as E10.5 in homozygous transgenic mice. Apparent agenesis of the lateral semicircular canal was evident at E14.5. Anomalies of nasomaxillary structures and olfactory neuroepithelium were present in heterozygous and homozygous transgenic mice. The 9257 mutation provides a model for analysis of the morphogenesis of these three neurosensory systems and their associated bony structures.

Abnormalities, Multiple↗