Deer mice: "The Drosophila of North American mammalogy".
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Animals↗
Biomedical subjects
W D Dawson
Publications and source records attributed to W D Dawson.
Mus and Peromyscus chromosome homology established by FISH with three mouse paint probes.
Fluorescence-labeled DNA probes constructed from three whole house mouse (Mus domesticus) chromosomes were hybridized to metaphase spreads from deer mouse (Peromyscus maniculatus) to identify homologies between the species. Mus Chr 7 probe hybridized strongly to the ad-centromeric two-thirds of Peromyscus Chr 1q. Most of Mus 3 probe hybridized principally to two disjunct segments of Peromyscus Chr 3. Mus Chr 9 probe hybridized entirely to the whole Peromyscus Chr 7. Three Peromyscus linkage groups were assigned to chromosomes, based on linkage homology with Mus. The data also are useful in interpretation of chromosomal evolutionary history in myomorphic rodents.
Animals↗
Assignment of Tp53 and Tk1 to chromosome 13 in Peromyscus by fluorescence in situ hybridization.
Mus domesticus DNA probes for the tumor suppressor protein-53 (Tp53) and thymidine kinase-1 (Tk1) genetic loci were used to identify clones representing these loci in a Peromyscus leucopus (white-footed mouse) cosmid library. The cosmid-derived homologous probes were biotinylated and hybridized to P. maniculatus (deer mouse) chromosomes. Probes for both genes hybridized to the chromosome 13 pair identified by prior G-banding. Deer mouse chromosome 13 shares a region of homology with mouse chromosome 11, rat chromosome 10 and human chromosome 17.
Animals↗
Growth regulation in Peromyscus species hybrids: a test for mitochondrial-nuclear genomic interaction.
Interspecific hybridization of Peromyscus maniculatus (deer mouse) and P. polionotus (oldfield mouse) is accompanied by pronounced size differences between reciprocal F1 animals beginning in the fetus and continuing throughout life. Since the mitochondrial genome is inherited through the maternal line in Peromyscus, we tested the hypothesis that increased disparity between the species sources of mitochondrial and nuclear genomes within animals would exaggerate the reciprocal size effects through misregulation of growth, whereas species-compatible genomes were postulated to diminish the effect. Four series of backcrosses were established from females of the two reciprocal F1, while insuring continuity of the maternal mitochondrial composition at each generation. Size and weight measurements were made on neonatal, ten-day and six-month old animals through four or more backcross generations. Contrary to the hypothesis, deer mice with P. polionotus mitochondrial DNA, but 98% or more P. maniculatus nuclear composition, and animals with P. maniculatus mitochondria and principally P. polionotus nuclear genome regressed in mean size parameters to those of P. maniculatus and P. polionotus, respectively. Most of the regression was accounted for by the second backcross generation, and second and later backcross progeny did not differ significantly from the respective parental species controls. Maternal inheritance of mitochondrial DNA was confirmed by restriction enzyme analysis at the second and fifth backcross generation. Hybrid maternal effects in this Peromyscus cross are likely attributable to mechanisms other than nuclear-mitochondrial genomic interaction.
Animals↗
The evolution of coexisting highly divergent LINE-1 subfamilies within the rodent genus Peromyscus.
Two distinct members of the LINE-1 (L1) family in Peromyscus were characterized. The two clones, denoted L1Pm55 and L1Pm62, were 1.5 kb and 1.8 kb in length, respectively, and align to the identical region of the L1 sequence of Mus domesticus. Sequence similarity was on the order of 70% between L1Pm55 and L1Pm62, which approximates that between either Peromyscus sequence and Mus L1. L1Pm62 represents a more prevalent subfamily than L1Pm55. L1Pm62 exists in about 500 copies per haploid genome, while L1Pm55 exists in about 100 copies. The existence of major and minor subpopulations of L1 within Peromyscus is in contrast to murine rodents and higher primates, where L1 copy number is on the order of 20,000 to 100,000, and where levels of intraspecific divergence among L1 elements are typically less than 15-20%. Additional Peromyscus clones are similarly divergent from both L1Pm62 and L1Pm55, implying the existence of more than two distinct L1 subfamilies. The highly divergent L1 subfamilies in Peromyscus apparently have been evolving independently for more than 25 million years, preceding the divergence of cricetine and murine rodents. Investigations of the evolution of L1 within Peromyscus by restriction and Southern analysis was performed using species groups represented by the partially interfertile species pairs P. maniculatus-P. polionotus, P. leucopus-P. gossypinus, and P. truei-P. difficilis of the nominate subgenus and P. californicus of the Haplomylomys subgenus. Changes in L1 and species group taxonomic boundaries frequently coincided. The implications for phylogeny are discussed.
Animals↗
Inheritance of burrow building in Peromyscus.
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Animals↗
Biphasic response of Na+-dependent amino acid transport to tumor promoting phorbol esters in cultured renal epithelial cells, LLC-PK1.
Confluent, nongrowing renal epithelial cells, LLC-PK1, have a low rate of Na+-dependent (A-system) amino acid transport. Following a brief period of amino acid and serum deprivation, but with glucose provided as an energy source, such cells respond to the tumor promoter TPA with a brief enhancement of A-system activity that returns to control levels within 10-20 min. The response is followed some 30 min later by a large and prolonged elevation of transport activity (delayed response). The responses may be related to an increased amino acid requirement in mitogenized cells. The initial transport response appears to be the consequence of a protein kinase C-dependent phosphorylation event, phosphorylating either a regulator or the transporter itself, while the delayed response is dependent on the synthesis of new protein. The delayed transport response may also be dependent upon an early phosphorylation event, although apparently less directly than the early transport response. Several candidate proteins that might be involved in the regulation of the response(s) may be seen when electrophoretically separated cell proteins are examined for 32P or [35S]methionine incorporation after TPA treatment.
Amino Acids↗
Energetics of Na+-dependent amino acid co-transport in Ehrlich ascites tumor cells.
The energy available from the Na+ electrochemical potential gradient (delta mu Na) has been evaluated in Ehrlich ascites tumor cells during accumulation of 2-aminoisobutyric acid. Cells were incubated in media of varying [Na+] (25-154 mM) in the presence of 0.25 mM 2-aminoisobutyric acid to establish maximum steady-state accumulation of the amino acid. Membrane potential (Vm) and intracellular Na+ activity (aNa) were estimated using standard electrophysiological techniques. In physiological saline ([Na+] = 154 mM) aNa is 4.4 +/- 0.6 mM, giving an apparent Na+ activity coefficient (gamma app) in the cytoplasm of 0.17 +/- 0.02. Vm under these conditions is -20.8 +/- 2.1 mV. From these values, delta mu Na = 9.9 +/- 0.8 kJ/mol. Concomitant determinations of 2-aminoisobutyric acid (AIB) accumulation show an energy requirement (delta mu AIB) of 8.5 +/- 0.5 kJ/mol. Stepwise reductions in extracellular [Na+] give parallel reductions in aNa, Vm and 2-aminoisobutyric acid accumulation. However, under all conditions tested the energy available from the Na+ electrochemical potential gradient exceeds that needed to drive 2-aminoisobutyric acid uptake. The effects of 2-aminoisobutyric acid on Vm have also been determined. Addition of AIB (10 mM) to steady-state cells leads to membrane depolarization (resting Vm = -22.1 +/- 1.3 mV; plus AIB Vm = -16.2 +/- 1.2 mV) within 1 min. Subsequent repolarization of the membrane to resting levels occurs within 10 min. The repolarization phase is blocked in the presence of ouabain (2 mM). The results establish that the energy available from the Na+ gradient is sufficient to serve as a source for 2-aminoisobutyric acid accumulation.
Amino Acids↗
Parallel changes in amino acid transport and protein kinase C localization in LLC-PK1 cells treated with TPA or diradylglycerols.
Protein kinase C is considered to be a major target for tumor promoting phorbol esters such as 12-0-tetradecanoylphorbol-13-acetate (TPA). We have analyzed the correlation between A-system amino acid transport and the distribution of protein kinase C (PKC) between a membrane-rich fraction (100,000 g pellet) and cytosol (supernatant) from homogenized LLC-PK1 cells, a pig kidney epithelial cell line grown in culture. During log growth 1 day after seeding the cells onto culture plates, PKC activity is high in the membrane fraction and low in the cytosol. As the cells become confluent the PKC distribution shifts to a cytosolic pool. Concomitantly, A-system amino acid transport, as measured by methylaminoisobutyric acid [14C]MeAIB uptake, decreases. TPA (0.01-1.0 microM) induces a shift of PKC activity from the cytosol back to the membrane-rich fraction in post-confluent cells with a concomitant 2-3 fold stimulation of MeAIB uptake. The same responses can be achieved by treating cells with certain diradylglycerols, either diacylglycerols such as 1-oleyl-2-acetyl-sn-glycerol (OAG) or alkylacylglycerols such as 1-hexadecenyl-2-oleyl-sn-glycerol. Both responses to TPA are blocked by cytochalasin B, but cycloheximide inhibits the transport response without affecting PKC redistribution. It is suggested that the redistribution may be a necessary but not sufficient concomitant to the transport activation.
Amino Acids↗
Intracellular Na+, K+ and Cl- activities in Ehrlich ascites tumor cells.
Ehrlich ascites tumor cell membrane potential (Vm) and intracellular Na+, K+ and Cl- activities were measured under steady-state conditions in normal saline medium (Na+ = 154, K+ = 6, Cl- 150 mequiv./l). Membrane potential was estimated to be -23.3 +/- 0.8 mV using glass microelectrodes. Intracellular ion activities were estimated with similar glass electrodes rendered ion-selective by incorporation of ion-specific ionophores. Measurements of Vm and ion-activity differences were made in the same populations of cells. Under these conditions the intracellular Na+, K+ and Cl- activities are 4.6 +/- 0.5; 68.3 +/- 8.0; and 43.6 +/- 2.1 mequiv./l, respectively. The apparent activity coefficients for Na+ and K+ are 0.18 +/- 0.02 and 0.41 +/- 0.05 respectively. These are significantly lower than the activity coefficients expected for the ions in physiological salt solutions (0.71 and 0.73, respectively). The activity coefficient for intracellular Cl- (0.67 +/- 0.03), however, is close to that of the medium (0.73), and the transmembrane electrochemical potential difference for Cl- is not different from zero. The results establish that the energy available from the Na+ electrochemical gradient is much greater than previously estimated from chemical measurements.
Animals↗
Paternal antigen and progesterone effects on conceptus size in laboratory mice.
Reports in the scientific literature conflict regarding the possible effects of immunizing mothers with paternal antigens on placental and fetal size of the progeny. Several investigators noted an enhancement effect, while others were unable to demonstrate any effect or found an inhibitory influence. The principal differences among these previous experiments were in dosage and frequency of administration of antigen. A series of mice (C57BL/6J females immunized against A/J-strain male spleen cells and the reciprocal) was tested over a broad range of dosages, including repetitions of those given previously by other workers. Late-gestation conceptus weights and other measurements were negatively but highly correlated, with the loge of total paternal spleen cells used for preimmunization. However, the preimmunization effect could be nullified by treatment with medroxyprogesterone during pregnancy. Prior impregnation by males of the spleen-cell donor strain also countered the preimmunization inhibition of conceptus growth. Preimmunization dosage differences do not account for discrepancies observed by previous investigators.
Animals↗
Development of Na+-dependent hexose transport in cultured renal epithelial cells (LLC-PK1).
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Aminoisobutyric Acids↗
The use of HgCl2 to evaluate the cosubstrate: amino acid transport stoichiometry in Ehrlich ascites tumor cells.
Recent investigations have indicated that cellular rheogenic properties may interfere with the correct estimation of Na+ and amino transport stoichiometry. We have reevaluated the stoichiometry of Na+ and alpha-aminoisobutyric acid (alpha-AIB) cotransport in Ehrlich ascites tumor cells depleted of Na+ and ATP by incubation in Na+-free HEPES-buffered medium (pH 7.2) containing 160 mM K+ and 2.5 microM valinomycin. Transfer of the cells to a medium with 10 mM 22Na+, 10 mM 3H-AIB, and 150 mM K+ resulted in an enhancement of Na+ flux above basal levels, which represents 0.6 of the AIB uptake. Under these conditions the membrane potential, -7.0 +/- 0.1 mV (SEM), does not change with the addition of AIB, -7.3 +/- 0.6 mV (SEM). HgCl2 (10 microM) added to the medium inhibited AIB flux and AIB-stimulated Na+ flux by 45-50% but did not change the coupling ratio. HgCl2 (10 microM) does not inhibit the basal Na+ flux nor does it affect cellular Na+ or K+ content. In physiological medium cotransport is electrogenic. The membrane potential of Ehrlich cells in physiological medium is -22.3 +/- 0.8 mV (SEM) and depolarizes to -16.7 +/- 0.7 mV (SEM) upon addition of AIB. Under these conditions the coupling ratio was highly variable but the ratio of codepression is 0.90 +/- 0.02 (SEM) in the presence of HgCl2 (10 microM). These results are consistent with a model (Smith and Robinson, 1981) in which the stoichiometry is one cosubstrate molecule per molecule of alpha-AIB. We suggest that H+ provides the alternative cosubstrate in this low Na+ environment and that in high Na+ medium the Na+:AIB stoichiometry approaches 1:1.
Amino Acids↗
Medroxyprogesterone, immunosuppression, and conceptus size in Peromyscus.
Effects of exogenous medroxyprogesterone acetate (MPA) on skin transplant retention and conceptus size were studied in the deer mouse, Peromyscus maniculatus, and the oldfield mouse Peromyscus polionotus. Daily injections of 2 mg MPA significantly prolonged survival of allografts in P. maniculatus and transspecific grafts between P. maniculatus and P. polionotus. Allografts were retained significantly longer than transspecific grafts (17.2 vs 12.4 days) on MPA-treated P. maniculatus. Near-term fetal and placental sizes and weights were not detectably influenced by daily 1-mg MPA injections given to the mother from the 5th through the 19th day of pregnancy. The data are discussed relative to the possible immunosuppressive role of progestins in protecting the allogeneic conceptus from maternal immune rejection.
Animals↗
Linkage relationships among eleven biochemical loci in Peromyscus.
Interspecific F1 hybrids of Peromyscus maniculatus (deermice) and P. polionotus (oldfield mice) were backcrossed to P. maniculatus. Backcross progeny were electrophoretically typed for 11 variant protein markers: albumin, transferrin, leucine aminopeptidase, amylase, 6-phosphogluconate dehydrogenase, nucleoside phosphorylase, dipeptidase, tripeptidase, glutamate oxaloacetate transaminase, alcohol dehydrogenase, and sorbitol dehydrogenase. Genetic variation for each protein was attributed to a single autosomal locus. The alcohol dehydrogenase (Adh), salivary amylase (Amy), and albumin (Alb) loci appeared to be linked in the sequence of Adh-11.5 cM-Amy-33.3 cM-Alb. The tripeptidase locus, Pep-2, also may be loosely linked to Alb in this group. Variants at all other loci assorted independently. These and other known linkage relationships in Peromyscus correspond closely to those of the house mouse, Mus musculus. The available evidence in Peromyscus further supports the concept of linkage conservation by natural selection.
Albumins↗
Comparative progesterone concentrations in two Peromyscus species.
1. Plasma progesterone concentrations were measured by radioimmunoassay in the oldfield mouse (Peromyscus polionotus) and the deermouse (P. maniculatus) at estrus and at 5-day intervals during pregnancy. 2. P. polionotus had significantly higher progesterone levels, both at estrus and during gestation. 3. The level was markedly less in female P. polionotus bearing interspecific (P. polionotus x P. maniculatus) hybrid conceptuses than in those with conspecific conceptuses. 4. It is postulated that the reduced progesterone level in females bearing hybrid fetuses may be responsible for reproductive failure which regularly occurs when this cross is attempted. 5. An endocrine difference of this magnitude could represent an incipient reproductive isolating mechanism.
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Immunological factors in Peromyscus speciation.
Reciprocal interspecific F1 hybrids of deermice (Peromyscus maniculatus) and oldfield mice (P. polionotus) differ significantly and substantially in fetal and placental, as well as adult, size and weight. Hybrid fetal mortality is associated with large conceptus size. Skin grafts were exchanged between and within the two species to ascertain whether any relationship exists between mean graft retention time and body size of fetuses and adults. P. maniculatus skin grafted to P. polionotus rejected significantly earlier than the reciprocal xenograft. All interspecific graft combinations rejected significantly earlier than intraspecific grafts. Pre-immunization of female P. maniculatus with con- and trans-specific paternal spleen cell antigens reduced fetal, placental, neonatal, and ten-day size compared with controls. Size, weight, fertility, and graft rejection data were compared with several theoretical models. The data were consistent with the hypothesis that immunological disparity between the species could produce marked size variations in reciprocal hybrids. Multiple minor histocompatibility factors can account for large placental size and fetal mortality in Peromyscus hybrids. Physiological reproductive isolation may result from immunological differences between closely allied species.
Animals↗
Comparative genetics of hamster amylases.
Syrian (Mesocricetus auratus) and Chinese (Cricetulus griseus) hamsters were phenotyped by electrophoresis for salivary and pancreatic amylases. Syrian hamsters possess two salivary amylase electromorphs, the more anodal (fast) being invariant in 250 outbred and 17 representatives of 5 highly inbred lines. The slow electromorph had activity equal to that of the fast amylase (heavy), or had distinctly less activity (light), or was absent (null). The slow electromorph is inherited as an autosomal semidominant trait with two alleles. Amys and Amyo. Amys homozygotes produce heavy, Amyo homozygotes null, and heterozygotes light phenotypes, respectively. Five inbred strains of hamsters were homozygous Amyo. Pancreatic amylase was monomorphic. Eight outbred Chinese hamsters showed no salivary amylase activity with electrophoresis, but slight activity with long incubation on starch-agar plates. However, pancreatic amylase activity in the Chinese hamster exceeded that in Syrian hamsters. Site duplication and apparent "null" alleles for amylase genes occur in muroid rodents. The evolutionary implications are discussed.
Amylases↗