Biomedical subjects

F G Berger

Publications and source records attributed to F G Berger.

64 records · Page 4Linked to original sources

PubMed1984

The acute phase response of mouse liver. Genetic analysis of the major acute phase reactants.

We have examined changes in translatable liver mRNAs during the acute phase response in several inbred mouse strains. Induction of mRNAs for the known acute phase reactants serum amyloid A, hemopexin, haptoglobin, and alpha 1-acid glycoprotein was observed. Two alpha 1-acid glycoproteins, termed AGP-1 and AGP-2, differing in size and charge, were found in all mice and appear to derive from distinct yet closely related mRNAs. Polymorphism in the structure of AGP-1 among strains was used to map the structural gene, Agp-1, to chromosome 4 near the b locus. Structural variation for serum amyloid A enabled mapping its structural gene, S alpha alpha, to chromosome 7, near Gpi-1. A wild-derived population of mice, Mus spretus, contains several variations of interest, including structural variations in many acute phase proteins and a putative regulatory variation specific to AGP-1. Further analysis of these genetic variants should provide novel insights into the acute phase response and the factors that mediate it.

Animals↗

PubMed1983

Studies on genetic variation in major urinary protein synthesis in mouse liver.

A two- to fourfold difference in the relative rate of total major urinary protein (MUP) synthesis between C57BL/6J and C3H/HeJ female mice has been analyzed at the genetic and molecular levels. The C57BL/6J phenotype is dominant in F1 female progeny of a cross between the two strains. Quantitation of MUP mRNA levels indicates that the rate of synthesis variation does not reflect a change in the concentration of total MUP mRNA. In recombinant inbred strains derived from C57BL/6J and C3H/HeJ progenitors, the rate of synthesis difference segregates as a single genetic determinant that is not linked to the Mup-a locus on chromosome 4. The results suggest an unlinked locus that acts to alter total MUP synthesis without altering total MUP mRNA levels. Two models are proposed to describe the action of this locus, both of which imply some sort of posttranscriptional control of MUP synthesis.

Animals↗

PubMed1983

DNA sequence polymorphism in an androgen-regulated gene is associated with alteration in the encoded RNAs.

We have used plasmid pMK908, whose cDNA insert corresponds to an androgen-inducible RNA from mouse kidney, as a probe to study both the complementary genomic DNA and the encoded RNA sequences in several inbred strains of mice. A polymorphism in the 908 structural gene, revealed by Southern blotting of HindIII-generated DNA fragments, was found to map near the Gpi-1 and Tam-1 loci on chromosome 7. The 908 structural gene has been termed RP2. The 908 RNAs constitute a sequence-related group displaying extensive size heterogeneity. This heterogeneity, reflected in the size distribution of the RNA on electrophoretic blots, is controlled by a genetic site that is tightly linked to RP2. Thus, associated with polymorphism at RP2 is a change in the molecular size pattern of encoded transcripts.

Alleles↗

PubMed1981

Isolation and characterization of a DNA sequence complementary to an androgen-inducible messenger RNA from mouse kidney.

Clones containing sequences corresponding to testosterone-inducible RNAs of mouse kidney have been identified within a cDNA clone bank prepared from size-fractionated poly(A)-containing kidney RNA. A novel screening method was employed to specifically detect such sequences. One of these, pMK908, containing a 1.2 kilobase pair insert, was studied in detail. RNA blotting experiments show that the inserted DNA of pMK908 hybridizes to two kidney-specific RNA sequences, 2500 and 1500 nucleotides in length, both of which are rapidly induced by testosterone treatment of female mice in vivo. RNA excess hybridization studies reveal that these RNAs constitute approximately 0.004% of th total RNA population in female kidneys and are induced approximately 7-8-fold by testosterone. The RNA has been isolated and translated in a cell-free system and encodes a 43,000-dalton polypeptide chain. The induction of these RNAs by testosterone is independent of the pituitary gland, but does depend upon the testosterone receptor protein. The existence of pMK908, and other chimeric plasmids containing testosterone-inducible sequences, should be valuable in understanding the response of the mouse kidney to androgens.

Animals↗

PubMed1981

Biosynthesis of the major urinary proteins in mouse liver: a biochemical genetic study.

By labeling liver protein in vivo with [3H] leucine, the relative biosynthetic rate has been measured for the major urinary proteins (MUPs), three closely related, androgen-regulated proteins that are synthesized in mouse liver, secreted into the bloodstream, and excreted into the urine. In livers from females of strain C57BL/6J, total MUP synthesis represents about 0.6-0.9% of the total protein synthesis; in males and testosterone-treated females of the same strain, synthesis increases to about 3.5-4.0% of the total. This 4- to 6-fold induction of total MUP synthesis is similar to the androgen-mediated increase in MUP-specific messenger RNA reported by others, and indicates that the previously observed 20- to 25-fold induction of total MUP excretion into urine is generated partly at the posttranslational level. By measuring the ratio of synthesis of the individual MUPs, it was determined that the testosterone-mediated change in the pattern of MUP synthesis, indicating nature, of MUPs excreted. A survey of seven inbred mouse strains revealed polymorphism for the rate of total MUP synthesis in untreated females. Two classes could be distinguished on the basis of a 3-to 5-fold difference in the rate. This variation does not correlate with variation at Mup-a, a locus that controls the ratio of the three MUPs in urine from androgen-induced mice. These findings are consistent with the notion that MUP expression is controlled by a variety of independently assorting genes.

Animals↗

PubMed1979

Cis-active control of mouse beta-galactosidase biosynthesis by a systemic regulatory locus.

Several higher organisms have been reported in which enzyme levels are determined genetically by sites located in close proximity to the corresponding structural genes. In several cases, these sites have been shown to act by controlling the rates of enzyme synthesis. Cis compared with trans action has been tested for those proximate regulatory sites controlling enzymes for which appropriate structural variants exist. The rate of synthesis of beta-galactosidase in mouse tissues is under the control of a regulatory locus; Bgl-s, that is tightly linked to the enzyme structural gene; we have tested the cis/trans nature of Bgl-s action by analysis of the electrophoretic mobility of the enzyme from animals heterozygous for the appropriate regulatory and structural alleles. Our results indicate that Bgl-s acts cis, controlling the expression of the structural gene located on the same chromosome.

Animals↗

PubMed1979

Genetic determination of the developmental program for mouse liver beta-galactosidase: involvement of sites proximate to and distant from the structural gene.

The identification and mode of action of genetic loci that program gene expression during development are important for understanding differentiation in higher organisms. Previous work from this laboratory has identified two patterns for the postnatal development of liver beta-galactosidase among inbred mouse strains: type I, where activity levels remain constant after about 30 days of age, is found in strains DBA/2J, CBA/J, and BALB/cJ, among others; type II, where activity levels increase between 25 and 50 days of age to reach a new adult level, is found in strain C57BL/6J and related strains. It has been shown that the type I vs. type II developmental difference between strains C57BL/6J and DBA/2J is due to variation at a locus, Bgl-t, that maps with the beta-galactosidase complex, [Bgl], on chromosome 9. In the present study, we have confirmed the existence of Bgl-t as a temporal locus within [Bgl] by analysis of both a congenic strain carrying the beta-galactosidase complex of strain CBA/J in the C57BL/6J genetic background and a cross of strains CBA/J and C57BL/6J. The existence of additional temporal loci for beta-galactosidase that segregate independently of the structural gene and participate in determination of the type I vs. type II difference was revealed by analysis of: (1) a congenic strain containing the beta-galactosidase complex of strain BALB/cJ in the C57BL/10Sn background; (2) recombinant inbred lines derived from progenitor strains C57BL/6ByJ and BALB/cByJ; and (3) a genetic cross between strains C57BL/6ByJ and BALB/cByJ. Thus, for these pairs of strains, the type I vs. type II developmental difference is due to variation at a temporal locus (or loci) unlinked to the enzyme structural gene, and not at Bgl-t. These facts, together with information gathered from an examination of the distribution of beta-galactosidase phenotypes among over 100 inbred strains (Breen, Lusis and Paigen 1977), have led us to conclude that the postnatal developmental pattern for liver beta-galactosidase is determined by a set of interacting temporal genes. One of these, Bgl-t, is located within [Bgl], and one or more are separable from [Bgl] by recombination. A possible mode of interaction among the temporal and instructural loci is suggested.

Animals↗

PubMed1978

Regulation of the rate of beta-galactosidase synthese by the Bgs and Bgt loci in the mouse.

We have developed an assay for the in vivo rate of beta-galactosidase synthesis in mouse tissues to assess the mechanism by which the Bgs and Bgt loci regulate activity levels of this enzyme. Genetically determined differences in liver and kidney beta-galactosidase content reflect equivalent differences in specific rates of enzyme synthesis. We conclude that Bgs and Bgt regulate beta-galactosidase activity by controlling the rate of synthesis of the beta-galactosidase molecule.

Alleles↗

PubMed1978

Relationship between genetic variation in thermal stability and electrophoretic mobility of mouse beta-galactosidase.

We have examined the relationships between the genetic determinants for mouse beta-galactosidase heat stability and electrophoretic mobility, in order to clarify previous reports indicating that a variation for enzyme heat stability is restricted to kidney while that for electrophoretic mobility is expressed in all tissues. We find that the two phenotypes show concordant strain distributions and cosegregate in genetic crosses. In contrast to a previous report, the thermal stability variation is expressed in all tissues, although the absolute rate of enzyme inactivation is tissue specific. The evidence supports the notion that a single beta-galactosidase structural locus is expressed in all tissues and that the differences in enzyme stability between tissues results from posttranslational enzyme modification.

Animals↗

PubMed1975

Tryptophan synthetase alpha(5.7-S): novel molecular species formed within Escherichia coli.

A novel molecular species contributes about 5% of the total tryptophan synthetase of Escherichia coli derepressed for the trp operon enzymes. The new species is identified under conditions in which the dissociation of the two nonidentical subunits of the tryptophan synthetase complex is favored. The new species sediments at 5.7S, catalyzes the conversion of indole-3-glycerol phosphate to indole, and has been designated alpha(5.7-S). Although alpha(5.7-S) is not observed in extracts of trpA or trpB mutant strains deficient in the ability to form tryptophan synthetase alpha or beta2 subunits, respectively, a mixture of the two extracts allows the formation of alpha(5.7-S). Similar results are obtained when a homogeneous alpha protein is mixed with an extract of a trpA mutant strain, suggesting that the interaction of alpha and beta2 proteins is obligatory for alpha(5.7-S) formation. One can obtain a beta2 protein preparation that when mixed with a pure alpha protein gives no alpha(5.7-S). Therefore, the interaction of alpha and beta2 proteins alone is not sufficient for the formation of alpha(5.7-S). When a mixture of alpha and beta2 proteins devoid of alpha(5.7-S) is added to extracts of trp deletion mutants, the novel species can be reconstituted in vitro only when deletions are used that carry at least the operator-proximal part of the trpB gene. Therefore, it is concluded that the alpha(5.7-S) species of tryptophan synthetase results from the interaction of the alpha protein, the beta2 protein, and a third component, beta', specified by the deoxyribonucleic acid defined by the end points of two trp deletion mutants.

Cell-Free System↗