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J B Whitney

Publications and source records attributed to J B Whitney.

At least 37 records · Page 2Linked to original sources
PubMed1986

Characterization and mapping of DNA sequence homologous to mouse U1a1 snRNA: localization on chromosome 11 near the Dlb-1 and Re loci.

A phage clone which contained a functional U1a1 snRNA gene was isolated from a mouse genomic library. A single copy fragment was isolated from the 3' flanking region of the U1a1 gene and used as a hybridization probe for Southern blotted DNAs from recombinant inbred strains of mice, mouse-hamster hybrid cells, and the offspring from backcrosses between BALB/c mice and mice which were heterozygous for the Rex (Re) marker. The results of these experiments prove that the U1a1 gene is located on chromosome 11 near the Delb-1 and Re loci.

Animals↗
PubMed1985

Detection of neutral amino acid substitutions in proteins.

The field of biochemical genetics relies heavily upon the detection by electrophoresis of genetically determined variants of proteins. Most of these variants differ by substitutions that involve charged amino acids. Genetic variants of another large class, ones that involve substitutions among neutral amino acids, are not easily detected and are often ignored. Ampholyte isoelectric focusing in some cases can separate proteins indistinguishable by standard electrophoresis, including genetic variants of mouse hemoglobins that differ only by neutral amino acid substitutions. A revolutionary variation of isoelectric focusing, in which gradients covering a small pH range are fixed into place in a polyacrylamide gel, provides greater resolution of these nearly identical proteins. Mouse hemoglobin tetramers that differ only by the substitution of alanine for glycine in the alpha-globin chains are resolved by several millimeters with the new technique; by comparison, these tetramers are imperfectly resolved on a standard pH 7-9 isoelectric focusing gel. This improved technique of isoelectric focusing was used to identify a variety of previously unreported genetic variants of mouse hemoglobin alpha chains. Immobilized gradients tailored to the requirements of the proteins being analyzed will extend greatly the ranges of protein variations that can be easily recognized for diverse applications, including genetic quality-control analyses and in studies of genetics, mutagenesis, and evolution.

Amino Acid Sequence↗
PubMed1985

Erbb is linked to the alpha-globin locus on mouse chromosome 11.

A fragment of the human gene for c-erb-B was used to map homologous sequences in mice. Analysis of somatic cell hybrids and recombinant inbred and congenic mouse strains indicated that this gene, designated Erbb, is closely linked to the gene for alpha-globin on mouse chromosome 11. Several genes controlling hematopoietic differentiation map to mouse chromosome 11.

Animals↗
PubMed1984

Novel carbonic anhydrase (Car-2) allele in Spanish mice.

A unique electrophoretic form of carbonic anhydrase is characteristic of some laboratory-maintained mice of the wild mouse species Mus spretus. This isozyme has been characterized by cellulose acetate electrophoresis and by isoelectric focusing. It is proposed that this isozyme be called CAR-2C and that its encoding allele be designated Car-2c. Fertile hybrids of Mus spretus and C57BL/6J (Car-2a) show both CAR-2A and CAR-2C bands of approximately equal intensity. The CAR-2C isozyme is readily identified by electrophoresis on 75-mm cellulose acetate strips because it migrates significantly faster than the isozymes of inbred mice, the CAR-2A and CAR-2B that do not separate from one another under standard conditions. Isoelectric focusing cleanly resolves all three of these CAR-2 forms. Mus hortulanus, although closely related to Mus spretus in other biochemical-genetic characteristics, has a CAR-2-homologous isozyme that is distinctly different from the CAR-2C of Mus spretus and from the isozymes of the common inbred strains.

Alleles↗
PubMed1982

The primary structure of genetic variants of mouse hemoglobin.

The primary structures of the alpha globins from CE/J, DBA/2J, and a stock of Potter's mice were determined to identify the amino acid substitutions associated with the unique isoelectric focusing patterns of these hemoglobins. In addition, the primary structures of the alpha globins from MOL III and PERU mice were studied in search of amino acid substitutions that may not be detected by isoelectric focusing. CE/J hemoglobin contains a unique kind of alpha globin called chain 5. It differs from the single kind of alpha globin (chain 1) in C57BL/6 by having alanine rather than glycine at position 78. DBA/2J hemoglobin has two kinds of alpha globins: one half is like chain 5 and the other half is like chain 1. The hemoglobin from Potter's stock of Mus musculus molossinus also contains chains 1 and 5, but they are expressed at different levels i.e., 80% chain 1 and 20% chain 5. MOL III hemoglobin has a single kind of a alpha globin identical to that in C57BL/6, and PERU hemoglobin contains approximately 40% chain 1 and 60% chain 4. Chains 1 and 4 have different amino acids at positions 25, 62 and 68. These studies confirm that mouse hemoglobins separable by isoelectric focusing, but not by other means of electrophoresis, have substitutions of neutrally charged amino acids in their alpha chains.

Amino Acid Sequence↗
PubMed1981

Mouse alpha-globin genes and alpha-globin-like pseudogenes are not syntenic.

A genetic polymorphism for a Bgl I endonuclease site near the alpha-globin-like pseudogene alpha-4 of C57BL/6 and C3H/HeN mice was used to show that alpha-4 was not affected by three independent mutations in which the adult globin genes alpha-1 and alpha-2 were deleted. These results indicated that alpha-4 might not be located adjacent to the adult alpha-globin genes on chromosome 11. Restriction endonuclease analysis of DNA of a primary clone of a Chinese hamster--mouse somatic cell hybrid that had lost mouse chromosomes 11 and 18 showed that this clone lacked the adult murine globin genes alpha-1 and alpha-2 but it did contain the alpha-globin-like pseudogenes alpha-3 and alpha-4. These results indicated that the adult alpha-globin genes and alpha-globin-like pseudogenes are not located on the same chromosome. Similar analyses of several other Chinese hamster--mouse somatic cell hybrids that had segregated other mouse chromosomes indicated that the alpha-globin-like pseudogenes alpha-3 and alpha-4 are located on mouse chromosomes 15 and 17, respectively. These data explain why alpha-3 and alpha-4 were not affected by the three independently induced deletion-type mutations that cause alpha-thalassemia in the mouse.

Animals↗
PubMed1981

Deletions in the alpha-globin gene complex in alpha-thalassemic mice.

Three induced, heritable mutations in the mouse cause alpha-thalassemias. The adult alpha-globin genes on each mutant chromosome are no longer expressed. Embryos heterozygous for one normal and any of the three mutant chromosomes also seem to be deficient in embryonic alpha-globin-like x-globin, suggesting that the x-globin gene is nearby and also inactivated. A normal genetic polymorphism for a specific EcoRI site in or around the mouse alpha-globin gene complex has been used here to show that each of the three mutated chromosomes has a deletion that includes the segment of a 12-kilobase EcoRI band which normally carries one of the two adult alpha-globin genes. The deletion of the comparable part of the second alpha-globin gene site is also inferred. Nonetheless, a 4.7-kilobase EcoRI segment which carries a characterized alpha-globin-like pseudogene is still present in each mutant. These mutations were recovered after triethylenemelamine or x-ray treatments.

Animals↗
PubMed1981

Three mouse models of human thalassemia.

Three types of mice with globin gene mutations, called 352HB, 27HB, and Hbath-J, appear to be true animal models of human thalassemia. Expression of the alpha-globin genes in three stocks of mice, each one heterozygous for one of the alpha-globin mutations, was examined at the polypeptide, RNA, and DNA levels. alpha-Globin polypeptide chains, relative to beta-globin chains in heterozygous thalassemic mice, are present at approximately 80% of normal. The ratios of alpha-globin to beta-globin RNA sequences are also 75-80% of normal, exactly reflecting the alpha-globin to beta-globin chain ratios. In the case of mutant 352HB, at least one alpha-globin gene is deleted. Thalassemic mouse erythroid cells appear to compensate partially for the loss of half of their alpha-globin genes.

Animals↗
PubMed1980

Linkage of genes for adult alpha-globin and embryonic alpha-like globin chains.

In alpha-thalassemia, the genetic locus for the alpha chains of adult hemoglobin is not expressed. We have examined the hemoglobins of a number of individual mouse embryos heterozygous for a particular alpha-thalassemia (Hbath-J) and find no decrease in the proportion of hemoglobins containing the alpha chain as compared to the hemoglobin containing the alpha-like embryonic globin chain. This result suggests that the locus for this embryonic alpha-like chain is inactivated or deleted in these embryos as well. Because a single mutational event inactivated adult and embryonic loci, we conclude that they are probably closely linked to one another on the same chromosome. We also present evidence that an unusual hemoglobin in the blood of these embryos is composed only of an embryonic beta-like chain, and is thus analogous to the hemoglobin H (beta 4 tetramer) of adult alpha-thalassemics.

Animals↗
PubMed1979

Resolution of products of the duplicated hemoglobin alpha-chain loci by isoelectric focusing.

Using a high-resolution isoelectric focusing system, we have been able to separate the products of the individual "nonallelic+ mouse hemoglobin alpha-chain genes. The hemoglobins of mice of inbred strains that make two structurally different, but electrophoretically identical, alpha chains resolve into two bands on isoelectric focusing. The hemoglobin from other strains that make only one type of alpha chain forms a single band. Two new "alleles" of haplotypes of Hba (the alpha-chain complex locus) are described that code for hemoglobins with solubilities similar to that of the hemoglobin of strain C57BL/6J, but that give demonstrably different isoelectric focusing patterns. Because this method allows Hba typing of strains with the Hbbd or "diffuse" allele at the hemoglobin beta-chain locus, we have also been able to classify a number of previously untyped stocks, including some recently derived from feral populations. Among these mice we have found new representatives of most of the extant Hba genotypes. The demonstration that it is possible to detect genetic differences involving only neutral amino acid substitutions between proteins suggest that careful application of appropriate isoelectric focusing systems to the analysis of other proteins will greatly increase the sensitivity of our ability to detect genetic variation.

Amino Acid Sequence↗
PubMed1978

Simplified typing of mouse hemoglobin (Hbb) phenotypes using cystamine.

Cellulose acetate electrophoresis of mouse hemoglobins modified with the disulfide reagent cystamine permits rapid, unequivocal discrimination of all combinations of the codominant mouse hemoglobin "single" (Hbbs) and "diffuse" (Hbbd and Hbbp) alleles. The single, diffuse major, diffuse d-minor, and diffuse p-minor adult hemoglobins are all resolved by this method, which depends on the presence of a cysteine in the beta chains of "diffuse" mice which is not found in the beta chain of "single" mice.

Alleles↗