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M Meisler

Publications and source records attributed to M Meisler.

At least 19 recordsLinked to original sources
PubMed1998

Identification of PKDL, a novel polycystic kidney disease 2-like gene whose murine homologue is deleted in mice with kidney and retinal defects.

Polycystin-1 and polycystin-2 are the products of PKD1 and PKD2, genes that are mutated in most cases of autosomal dominant polycystic kidney disease. Polycystin-2 shares approximately 46% homology with pore-forming domains of a number of cation channels. It has been suggested that polycystin-2 may function as a subunit of an ion channel whose activity is regulated by polycystin-1. Here we report the identification of a human gene, PKDL, which encodes a new member of the polycystin protein family designated polycystin-L. Polycystin-L has 50% amino acid sequence identity and 71% homology to polycystin-2 and has striking sequence and structural resemblance to the pore-forming alpha1 subunits of Ca2+ channels, suggesting that polycystin-L may function as a subunit of an ion channel. The full-length transcript of PKDL is expressed at high levels in fetal tissues, including kidney and liver, and down-regulated in adult tissues. PKDL was assigned to 10q24 by fluorescence in situ hybridization and is linked to D10S603 by radiation hybrid mapping. There is no evidence of linkage to PKDL in six ADPKD families that are unlinked to PKD1 or PKD2. The mouse homologue of PKDL is deleted in Krd mice, a deletion mutant with defects in the kidney and eye. We propose that PKDL is an excellent candidate for as yet unmapped cystic diseases in man and animals.

Amino Acid Sequence↗
PubMed1997

Mutation watch.

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Animals↗
PubMed1996

Genetic and physical mapping at the limb-girdle muscular dystrophy locus (LGMD2B) on chromosome 2p.

The limb-girdle muscular dystrophies (LGMD) are a genetically heterogeneous group of disorders, different forms of which have been mapped to at least six distinct genetic loci. We have mapped an autosomal recessive form of LGMD (LGMD2B) to chromosome 2p13. Two other conditions have been shown to map to this region or to the homologous region in mouse: a gene for a form of autosomal recessive distal muscular dystrophy, Miyoshi myopathy, shows linkage to the same markers on chromosome 2p as LGMD2B, and an autosomal recessive mouse mutation mnd2, in which there is rapidly progressive paralysis and muscle atrophy, has been mapped to mouse chromosome 6 to a region showing conserved synteny with human chromosome 2p12-p13. We have assembled a 6-cM YAC contig spanning the LGMD2B locus and have mapped seven genes and 13 anonymous polymorphic microsatellites to it. Using haplotype analysis in the linked families, we have narrowed our region of interest to a 0-cM interval between D2S2113 and D2S2112/D2S145, which does not overlap with the critical region for mnd2 in mouse. Use of these most closely linked markers will help to determine the relationship between LGMD2B and Miyoshi myopathy. YACs selected from our contig will be the starting point for the cloning of the LGMD2B gene and thereby establish the biological basis for this form of muscular dystrophy and its relationship with the other limb-girdle muscular dystrophies.

Animals↗
PubMed1984

Multiple non-allelic genes encoding pancreatic alpha-amylase of mouse are expressed in a strain-specific fashion.

The number of active Amy-2 genes has been estimated in strain CE/J mice which produce four distinct electrophoretic forms of alpha-amylase in their pancreas. cDNA cloning and DNA sequence analysis discloses five distinct mRNA sequences which differ by approximately 1% of their nucleotides. Two of these mRNAs specify the same protein. Changes in the nucleotide sequences result in amino acid replacements that alter the net charges of the deduced proteins. This has allowed a tentative assignment of individual mRNAs to isozymes detected by electrophoresis. Quantitative Southern blot hybridization using a DNA probe specific for the first exon of Amy-2 reveals the presence of greater than 10 Amy-2 related sequences per haploid CE/J genome. Models which could account for the mouse strain-specific differences with respect to the number of pancreatic alpha-amylase isozymes and their variable but genetically determined quantitative ratios are discussed.

Alleles↗
PubMed1982

Two distinct pancreatic amylase genes are active in YBR mice.

The genetic determinants of pancreatic amylase expression in YBR mice differ in two respects from those of other inbred strains. First, there are two nonallelic amylase isozymes present in YBR pancreas, while most mouse strains express a single pancreatic amylase protein. In addition, the in vivo rate of total pancreatic amylase synthesis is 50% of that in other strains. Both these traits are determined by genetic sites in the region of the Amy-2 locus on mouse chromosome 3. To determine the molecular basis for the presence of two isozymes in this strain, we have compared portions of their amino acid sequences. Two differences between isozymes A1 and B1 were identified among the 77 residues compared. This result demonstrates that two distinct amylase genes are expressed in YBR pancreas.

Amino Acid Sequence↗
PubMed1980

Morphologic and biochemical abnormalities of kidney lysosomes in mice with an inherited albinism.

The light-ear mutation in the mouse may serve as a useful model for the human inherited oculocutaneous albinisms such as the Hermansky-Pudlak and Chédiak-Higashi syndromes. The authors have investigated the kidney lysosomes of le/le mutant mice by histochemical methods. A striking increase in the staining reaction for the lysosomal enzymes beta-galactosidase and acid-phosphatase was evident in kidney cortex of the mutant mice, in comparison with +/+ controls. The lysosomal protease, cathepsin C, is also found to be elevated in the mutant. By light microscopy, there appeared to be an increase in the number of lysosomes in mutant kidney. Electron microscopy revealed the presence of large, multilamellar granules in proximal tubule cells. Analysis of sedimentation through sucrose gradients demonstrated the presence of a low-density population of lysosomes in the mutant kidney. In addition, a striking accumulation of ceroidlike pigment was observed. The molecular lesions responsible for the melanolysosomal syndromes in mice and man are still unidentified.

Albinism↗
PubMed1979

Cadmium metabolism in cdm/cdm mice.

The uptake and metabolism of cadmium by cadmium-susceptible (+/+) and cadmium-resistant (cdm/cdm) strains of mice have been compared. These strains did not differ with respect to the quantitative uptake of cadmium into liver, kidney, or testis. After intraperitoneal administration of a nontoxic dose, more than 80% of the cadmium in liver and testis of both strains is bound to low molecular weight proteins. The chromatographic behavior of these cadmium-binding proteins is not affected by cdm genotype.

Animals↗
PubMed1979

Genetic variation in amount of salivary amylase in the bank vole, Clethrionomys glareola.

Several investigated bank vole populations are polymorphis for the number of salivary amylase loci, and individual chromosomes may carry one, two or three linked amylase structural genes. In the present study, we have used bank vole stocks homozygous for different chromosomes to investigate the relationship between amylase production and gene number. By measuring the amylase activity in parotid glands and the percentage of amylase protein in saliva, we have been able to demonstrate that the amount of salivary amylase is directly proportional to the proposed gene number. The paper also describes the allele, AmySu, which codes for a heat-labile salivary amylase. The relative amounts of the heat-labile isozyme have been determined in different heterozygotes containing this allele, and these results also support the multiple locus model. Finally, a stock devoid of salivary amylase activity was established. Animals from this strain have, however, a protein in the parotid glands and in saliva that is very similar to amylase in molecular weight, amino acid composition and in its binding to glycogen and cyclohepta-amylose. In genetic crosses, the protein segregates as an amylase allele. Therefore, this protein, encoded by the functionally null allele AmyN, may represent an incorrectly processed amylase precursor.

Amylases↗
PubMed1976

Genetic determination of the beta-galactosidase developmental program in mouse liver.

The developmental program for beta-galactosidase in C57BL/6J and related strains of mice differs from that seen in most other mouse strains. Mice of the C57BL/6 group show a rise in liver enzyme activity during development that is not seen in mice of other strains. The developmental pattern of beta-galactosidase activity in heart and brain of C57BL/6 mice is similar to that in other strains. Physical, kinetic, and immunological tests indicate that the developmental increase in C57BL/6 enzyme activity is an increase in the number of molecules of the same species of enzyme protein that is present in other strains. In genetic crosses, the presence of the developmental rise in liver enzyme activity segregates as if determined by a single genetic factor showing additive expression in heterozygotes. This factor is closely linked to the beta-galactosidase structural gene on chromosome 9. The existence of a genetic variant with these properties is evidence that programmatic information capable of regulating the temporal expression of a structural gene can be encoded in DNA.

Animals↗
PubMed1975

Biochemical and immunological studies of purified mouse beta-galactosidase.

Beta-Galactosidase (EC 3.2.1.23) has been purified from the livers of C57BL/6J mice. The enzyme migrated as a single band of protein on polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The molecular weight of the denatured and reduced enzyme was 63,000. The native form of beta-galactosidase appeared to be a tetramer of 240,000 at pH 5.0, which was reversibly dissociated at alkaline pH to a dimer with apparent molecular weight of 113,000. Multiple charge isomers of beta-galactosidase were resolved by polyacrylamide gel electrophoresis and ion exchange chromatography. Treatment of beta-galactosidase with neuraminidase markedly reduced its electrophoretic mobility. Purified enzyme as well as crude liver extract hydrolyzed p-nitrophenyl-beta-D-fucoside at one-tenth the rate of hydrolysis of the beta-galactoside. Antiserum to the purified enzyme precipitated the major portion of beta-galactosidase activity of mouse liver, brain, and kidney. This antiserum cross-reacts with beta-galactosidases from rat and Chinese hamster, but not with human, porcine, or bovine beta-galactosidase.

Animals↗
PubMed1975

Activity of human hepatic beta-galactosidase toward natural glycosphingolipid substrates.

1. Human hepatic "acid" beta-galactosidase preparations, which had been purified approximately 250-fold, were examined for activities toward 4-methylumbelliferyl beta-galactoside, galactosylceramide, lactosylceramide, galactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosyl-glucosylceramide (GM1-Ganglioside) and galactosyl-Cacetylgalactosaminyl-galactosyl-glucosylceramide (asialo GM1-ganglioside). 2. The enzyme was active toward the synthetic substrate, GM1-ganglioside and asialo GM1-ganglioside but was inactive toward galactosylceramide. Under our assay conditions, optimized for lactosylceramidase II, the preparations were as active toward lactosylceramide as toward GM1-ganglioside or its asialo derivative. Teh apparent Km values for the three natural substrates were similar. When determined by the assay system of Wenger, D.A., Sattler, M., Clark, C. and McKelvey, H. (1974) Clin. Chim. Acta 56, 199-206, lactosylceramidecleaving activity was 0.2% of that determined by our assay system. This confirmed our previous suggestion that the Wenger assay system determines exclusively the activity of lactosylceramidase I, which is probably identical with galactosylceramide beta-galactosidase. 3. Crude sodium taurocholate was far more effective than pure taurocholate in stimualting hydrolysis of the three glycosphingolipids by the beta-galactosidase. However, crude tauroxycholate, suggesting that the unique activating capacity of the crude taurocholate might be due to taurodeoxycholate present as the major impurity. 4. Cl- was generally stimulatory for hydrolysis of the natural glycosphingolipids by our enzyme preparation. Effects of additional oleic acid and Triton X-100 Were generally minor in either direction. 5. When the enzyme preparation was diluted with water, activity toward the synthetic substrate declined rapidly while those toward the natural substrates were essentially stable. Activity toward the synthetic substrate remained much more stable when the enzyme was diluted with 0.1 M sodium citrate/phosphate buffer, pH 5.0. 6. These observations provide insight into the complex relationship among the human hepatic beta-galactosidases.

Chlorides↗