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PubMed2004

Organization of the main olfactory bulbs of some mammals: musk shrews, moles, hedgehogs, tree shrews, bats, mice, and rats.

We immunohistochemically examined the organization of the main olfactory bulbs (MOBs) in seven mammalian species, including moles, hedgehogs, tree shrews, bats, and mice as well as laboratory musk shrews and rats. We focused our investigation on two points: 1) whether nidi, particular spheroidal synaptic regions subjacent to glomeruli, which we previously reported for the laboratory musk shrew MOBs, are also present in other animals and 2) whether the compartmental organization of glomeruli and two types of periglomerular cells we proposed for the rat MOBs are general in other animals. The general laminar pattern was similar among these seven species, but discrete nidi and the nidal layer were recognized only in two insectivores, namely, the mole and laboratory musk shrew. Olfactory marker protein-immunoreactive (OMP-IR) axons extended beyond the limits of the glomerular layer (GL) into the superficial region of the external plexiform layer (EPL) or the nidal layer in the laboratory musk shrew, mole, hedgehog, and tree shrew but not in bat, mouse, and rat. We observed, in nidi and the nidal layer in the mole and laboratory musk shrew MOBs, only a few OMP-IR axons. In the hedgehog, another insectivore, OMP-IR processes extending from the glomeruli were scattered and intermingled with calbindin D28k-IR cells at the border between the GL and the EPL. In the superficial region of the EPL of the tree shrew MOBs, there were a small number of tiny glomerulus-like spheroidal structures where OMP-IR axons protruding from glomeruli were intermingled with dendritic branches of surrounding calbindin D28k-IR cells. Furthermore, we recognized the compartmental organization of glomeruli and two types of periglomerular cells in the MOBs of all of the mammals we examined. These structural features are therefore considered to be common and important organizational principles of the MOBs.

Animals↗
PubMed1992

Müller cells in vascular and avascular retinae: a survey of seven mammals.

Eight monoclonal antibodies were used to label Müller cells in four mammals that have vascular retinae (cats, dogs, humans, and rats) and in three with avascular retinae (echidnas, guinea pigs, and rabbits). Müller cells were found to have a fairly uniform retinal distribution in seven species, with a mean density of 8,000-13,000 cells mm-2. Müller cells in avascular retinae differ from their vascular counterparts in four respects. First, they are shorter than those in vascular retinae. This difference is mainly due to a reduction in the thickness of the outer nuclear layer. Second, the trunks of Müller cells in avascular retinae tend to be thicker, although those in echidnas are an exception to this trend. Third, Müller cell rootlets in avascular retinae follow a more tortuous course than those in vascular retinae, reflecting the fact that photoreceptor nuclei in the two types of retina have different shapes and stacking patterns. Fourth, due to a reduction in the density of photoreceptors in avascular retinae, there are fewer neurones per Müller cell. Although these four features may enable Müller cells to assist the nutrition of neurones in the inner layers of avascular retinae, they are unlikely to be morphological specializations that have evolved for that purpose. Rather, these features appear to be a direct consequence of the fact that avascular retinae are thinner and have a differently organised outer nuclear layer. These features aside, Müller cells in avascular retinae closely resemble their counterparts in vascular retinae.

Animals↗
PubMed1987

Developmental consequences of autosomal aneuploidy in mammals.

Autosomal aneuploidy in mammals adversely affects developmental processes. In human beings, for example, trisomy 21 is the most frequent aneuploidy detected among newborns and the most common known genetic cause of mental retardation. In this review, several hypotheses are discussed that have been proposed to explain the mechanisms by which aneuploidy (especially trisomy) disrupts development. These mechanisms included specific gene dosage effects, generalized disruption of genetic homeostasis, and the influence of the parental origin of the duplicated chromosome. The availability of specific chromosomal rearrangements in mice, coupled with selective breeding schemes, permits generation of aneuploidy of specific chromosomes or chromosomal segments on controlled genetic backgrounds, thus enabling the systematic study of the causes and consequences of defined aneuploidy. Phenotypic characteristics associated with a number of specific aneuploidies in the mouse are discussed. Emphasis is placed on the effects of trisomy 16. Genetic homology between mouse chromosome 16 and human chromosome 21 has led investigators to suggest that analogous mechanisms will be responsible for the developmental abnormalities produced in these respective aneuploidies. Analysis of trisomy 16 mice from the organismal to the subcellular level has revealed a number of phenotypic characteristics (particularly neurobiologic ones) shared with human trisomy 21. The dosage effects of shared genes (or their products) may contribute to the development of these features.

Aneuploidy↗
PubMed1994

Assessing the risk of heritable gene mutation in mammals: drosophila sex-linked recessive lethal test and tests measuring DNA damage and repair in mammalian germ cells.

The former U.S. EPA OPPT tiered test scheme for heritable gene mutations included the Drosophila sex-linked recessive lethal (SLRL) test in which positive results triggered the mouse specific locus (MSL) test. However, review of available literature indicated that the evaluation of mutations in the germ cells of this insect is not a good predictor of the risk of heritable gene mutations in mammals. The database contained 29 compounds for which there were conclusive MSL test results in either spermatogonial and/or postspermatogonial cells. Results in the SLRL test were available for 27 of those compounds. Of the 24 SLRL-positive chemicals, only 13 (54%) induced heritable mutations in mice; the three SLRL-negative compounds were nonmutagenic in mouse germ cells. The overall concordance between the two tests was 59%. In contrast, results of unscheduled DNA synthesis (UDS: 18 chemicals) and alkaline elution (AE: 14 chemicals) assays in rodent testicular cells following in vivo exposure correlated well with results in the MSL test (83% and 86%, respectively). MSL test results in spermatogonia and postspermatogonia were also compared separately to the SLRL, UDS, and AE assays. The concordances for the two cell types in the SLRL relative to the MSL test were 36% and 79%, respectively, indicating that the SLRL test is extremely poor in predicting heritable gene mutations in mammalian spermatogonia. Concordances for UDS and AE assays relative to MSL test results in spermatogonia (53% and 54%, respectively) and postspermatogonia (91% and 100%, respectively) were greater. Based on these analyses, the U.S. EPA OPPT has revised its tiered test scheme using assays for interaction with gonadal DNA (e.g., UDS and AE) in place of the SLRL test.

Animals↗
PubMed2003

Astrocytes as support for axonal regeneration in the central nervous system of mammals.

Reactive astrocytes are one of the main impediments for axonal regeneration in the central nervous system of mammals. Using mice KO for GFAP and vimentin, we show that reinnervation occurs after an hemisection of the spinal cord, mainly through sprouting of controlateral intact serotoninergic and cortico-spinal axons, thanks to the absence of glial reactivity. This reinnervation is paralleled by the restoration of impaired locomotion of the ipselateral hindleg. Future applications to spinal cord injured patients are discussed.

Animals↗
PubMedDate not supplied

Fluoride accumulation and toxicity in laboratory populations of wild small mammals and white mice.

A laboratory experiment was conducted to compare the toxicological response and metabolism of inorganic fluoride by three species of wild mammals and laboratory white mice (Mus musculus L.). The experimental populations of the wild species--the short-tailed field vole (Microtus agrestis L.), the bank vole (Clethrionomys glareolus L.) and the the wood mouse (Apodemus sylvaticus L.)--were laboratory reared from wild stock, and all test animals were exposed to 0, 40 or 80 microgram F per ml in their drinking water for up to 84 days. The 40 and 80 microgram F per ml treatments induced premature mortalities in M. agrestis and C. glareolus only. Differential intakes, absorption and retention of fluoride were evident between M. musculus and M. agrestis, the two species subject to cage studies of fluoride metabolism budgets. Interspecific variation in accumulation of fluoride with time was also evident between all four species as regards the femur, molars and incisors. Severe dental lesions were apparent in species surviving the 80 microgram ml(-1) treatment for 84 days. Overall, however, there were few clear differences in inherent species sensitivity to fluoride, the interspecific variation in metabolism and accumulation rates being attributable mainly to variation in intake.

Animals↗
PubMed1995

Ultrastructure and histochemistry of acid mucus glycoproteins in the estrous mammal oviduct.

The mucous surfaces of the oviducts of mammals, especially humans, are dependent on estradiol. The mucus glycoproteins and glycocalyceal glycoproteins have, however, barely been studied. Biochemical analyses have focussed on the relatively low molecular weight glycoproteins likely to be found in more serous-type granules of the ampulla and not on the very high MW glycoproteins typical of mucus and represented in the isthmus by morphological evidence of mucus secretion. Quantitatively, secretion from the ampulla is likely to predominate, because of its huge surface area compared with the isthmus. But functional closure of the isthmus under the influence of estradiol in the absence of progesterone means that it is the isthmus where luminal secretions accumulate--and where mucus glycoproteins will exert their most important effects on spermatozoa ascending the reproductive tract, and then on fertilized ova en route to the uterus. Further study of the extracellular, intraluminal, carbohydrate-rich environment of the oviductal isthmus, especially in humans, is likely to prove rewarding. Sampling of these secretions is now feasible using transvaginal, transuterine fallopian tube catheters that are in clinical use.

Animals↗
PubMed2003

Ontogenesis of the scapula in marsupial mammals, with special emphasis on perinatal stages of didelphids and remarks on the origin of the therian scapula.

The development of the scapula was studied in embryonic and postnatal specimens of Monodelphis domestica and perinatal specimens of Philander opossum, Caluromys philander, and Sminthopsis virginiae using histological sections and 3D reconstructions. Additionally, macerated skeletons of postnatal M. domestica were examined. This study focused on the detachment of the scapulocoracoid from the sternum and on the acquisition of a supraspinous fossa, a supraspinatus muscle, and a scapular spine, all these events associated with the origin of the therian shoulder girdle. In none of the specimens is there a continuity of the cartilaginous scapulocoracoid with the sternum, even though the structures are in close proximity, especially in S. virginiae. At birth, the first rib laterally presents a pronounced boss that probably contacts the humerus during certain movements. Only the acromial portion of the scapular spine, which originates from the anterior margin of the scapular blade, is preformed in cartilage. The other portion is formed by appositional bone ("Zuwachsknochen"), which expands from the perichondral ossification of the scapula into an intermuscular aponeurosis between the supra- and infraspinous muscles. This intermuscular aponeurosis inserts more or less in the middle of the lateral surface of the developing scapula. Thus, the floor of the supraspinous fossa is present from the beginning of scapular development, simultaneously with the infraspinous fossa. The homology of the therian spine with the anterior border of the sauropsid and monotreme scapula is questioned. We consider the dorsal portion (as opposed to the ventral or acromial portion) of the scapular spine a neomorphic structure of therian mammals.

Animals↗
PubMed1993

Immunoreactivity of PMP-22, P0, and other 19 to 28 kDa glycoproteins in peripheral nerve myelin of mammals and fish with HNK1 and related antibodies.

Mammalian peripheral nervous system (PNS) myelin contains several glycoproteins with molecular weights of 19 to 28 kDa, including the major 28 kDa P0 glycoprotein and a recently cloned protein called PMP-22. Some glycoproteins in this M(r) range in humans, cats and some other mammals react with HNK1, a mouse monoclonal antibody that identifies a carbohydrate epitope shared between the immune system and a number of adhesion proteins in the nervous system. A variety of antibodies to P0, PMP-22, and the carbohydrate determinants reacting with HNK1 were used to characterize immunochemically these 19 to 28 kDa glycoproteins of cat PNS myelin. The HNK1-reactive components include P0 and two slightly smaller 23 to 26 kDa proteins that are immunologically related to P0. However, HNK1 reacts most strongly with a lower molecular weight glycoprotein that does not react with the antibodies to P0 and was identified as PMP-22. Since the carbohydrate structure reacting with HNK1 is generally expressed on adhesion molecules, this result suggests that PMP-22 may function in cell-cell or membrane-membrane interactions. Furthermore, the related human anti-MAG monoclonal IgM antibodies from patients with neuropathy also react strongly with PMP-22, suggesting that it may be a target antigen in the pathogenesis of this disease. Purified PNS and CNS myelin from bony fish (toadfish and trout) were also shown to contain major glycoproteins, in the same 19 to 28 kDa M(r) range, that react very strongly with HNK1. It is shown that fish myelin has major proteins of this size that are immunologically and structurally related to mammalian P0, and it is demonstrated here that one of the strongly HNK1-positive proteins reacted well with an antiserum raised to bovine P0. The presence of high levels of the adhesion-related HNK1 epitope on these major myelin proteins of fish suggests that this carbohydrate structure may have played a role in the molecular evolution of myelin.

Animals↗
PubMed2003

Cytochrome c oxidase of mammals contains a testes-specific isoform of subunit VIb--the counterpart to testes-specific cytochrome c?

Sperm motility is highly dependent on aerobic energy metabolism, of which the apparent rate-limiting step of the mitochondrial respiratory chain is catalyzed by cytochrome c oxidase (COX). COX is the only electron transport chain complex to display isoforms, consistent with its suggested rate-limiting role. Isoforms were previously described for four of the 13 subunits. We now report the discovery that COX subunit VIb displays a testes-specific isoform in human, bull, rat, and mouse (COX VIb-2). Analysis of a variety of rat and mouse tissues, including ovaries, demonstrates exclusive expression of VIb-2 in testes, whereas VIb-1 transcripts are absent in rodent testes, even at early developmental stages. In contrast, both isoforms are transcribed in human testes. In situ hybridizations with human, rat, and mouse testes sections reveal VIb-2 transcripts in all testicular cell types. Within the seminiferous tubules, VIb-1 shows stronger signals in the periphery than in the lumen. Previously, cytochrome c was the only component of the mitochondrial respiratory chain known to express a testes-specific isoform in mammals. COX subunit VIb connects the two COX monomers into the physiological dimeric form, and is the only COX subunit that, like cytochrome c, is solely located in the inter-membrane space. Significant differences between the isoform sequences, in particular changes in charged amino acids, suggest interactions with cytochrome c and sperm-specific energy requirements.

Animals↗
PubMed1993

Sperm:egg ratios and putative molecular signals to modulate gamete interactions in polytocous mammals.

Reasoning from the premises that 1) the sperm:egg ratio at the time of activation of the secondary oocyte in mammals is close to unity under conditions of spontaneous mating, 2) a majority of eggs within the cumulus oophorus of a polytocous species is fertilized in a reasonably short interval of time, and 3) spermatozoa would find it difficult to reverse their approach to the zona pellucida, it is proposed that molecular gradients exist to divert spermatozoa penetrating the cumulus mass away from eggs already activated and towards eggs as yet unfertilized. Possible sources of such molecular cues are considered, as is the event that triggers their release.

Animals↗
PubMed2003

Saccharomyces cerevisiae QNS1 codes for NAD(+) synthetase that is functionally conserved in mammals.

NAD(+), an essential molecule involved in a variety of cellular processes, is synthesized through de novo and salvage pathways. NAD(+) synthetase catalyses the final step in both pathways. Here we show that this enzyme is encoded by the QNS1 gene in Saccharomyces cerevisiae. Expression of Escherichia coli or Bacillus subtilis NAD(+) synthetases was able to suppress the lethality of a qns1 deletion, while a B. subtilis NAD(+) synthetase mutant with lowered catalytic activity was not. Overexpression of QNS1 tagged with HA led to elevated levels of NAD(+) synthetase activity in yeast extracts, and this activity can be recovered by immunoprecipitation using anti-HA antibody. An allele of QNS1 was constructed that carries a point mutation predicted to reduce the catalytic activity. Overexpression of this allele, qns1(G521E), failed to elevate NAD(+) synthetase levels and qns1(G521E) could not rescue the lethality caused by the depletion of Qns1p. These results demonstrate that NAD(+) synthetase activity is essential for cell viability. A GFP-tagged version of Qns1p displayed a diffuse localization in both the nucleus and the cytosol. Finally, the rat homologue of QNS1 was cloned and shown to functionally replace yeast QNS1, indicating that NAD(+) synthetase is functionally conserved from bacteria to yeast and mammals.

Amide Synthases↗
PubMed1994

The nucleotide and deduced amino-acid sequences of a cDNA encoding lactate dehydrogenase from Caenorhabditis elegans: the evolutionary relationships of lactate dehydrogenases from mammals, birds, amphibian, fish, nematode, plants, bacteria, mycoplasma, and plasmodium.

The nucleotide and deduced amino-acid sequences of a cDNA encoding L-lactate dehydrogenase (LDH) from nematode, Caenorhabditis elegans, were reported. This first invertebrate LDH sequence of 333 amino acids, including the initiation methionine, exhibits 63% identity with that of the most primitive vertebrate lamprey. The evolutionary relationships among 36 LDH isozymes from mammals, birds, amphibian, fish, nematode, plants, bacteria, mycoplasma and plasmodium were analyzed. The invertebrate nematode LDH is evolutionarily positioned between plant LDH and mammalian testicular LDH-C isozymes. The mammalian LDH-C isozyme appears to have arisen after the invertebrate LDH, but prior to the divergence of vertebrate LDH-A (muscle) and LDH-B (heart) isozymes as described previously.

Amino Acid Sequence↗
PubMed1994

Chicken lacks the testis specific isozyme of angiotensin converting enzyme found in mammals.

Chicken angiotensin converting enzyme (ACE) cDNA was cloned based on homology to the mouse ACE sequence. The chicken ACE protein is highly homologous to the somatic isozyme of ACE found in human, mouse, bovine, and rabbit. Like the mammalian somatic forms, the chicken enzyme consists of two putative zinc binding sites at the center of two homologous domains. All known functional residues are absolutely conserved. Unlike the mammals, no evidence for a single domain, testis specific form of ACE was found in the chicken testis by either Northern blot or enzyme assay. This result is unexpected since the adult mammalian testis expresses one of the highest tissue levels of ACE.

Amino Acid Sequence↗
PubMed1997

A highly conserved major histocompatibility complex class I-related gene in mammals.

We report here a cDNA sequence of a murine homolog of the human major histocompatibility complex (MHC) class I-related gene, MR1. The analyses revealed unprecedentedly high conservation of MR1 in the alpha1 and alpha2 domains (corresponding to the peptide-binding domains in the classical MHC class I molecules) between human and mouse (predicted amino acid identity: 90 and 89% for the alpha1 and alpha2 domain, respectively), compared to MHC class I and other class I molecules. On the other hand, conservation in the alpha3 domain (73%) is comparable to those of others, suggesting domain-specific conservation of MR1. The localization of the mouse MR1 gene was determined to be chromosome 1H1, which corresponds to the human chromosomal region where the human MR1 gene is located (chromosome 1q25). High conservation of MR1 among mammals suggests that MR1 may be involved in critical conserved biological function(s).

Amino Acid Sequence↗
PubMed2002

Analysis of the role of RecQ helicases in RNAi in mammals.

The identity of mammalian genes involved in RNA interference (RNAi), the targeted sequence-specific mRNA degradation by double-stranded RNA (dsRNA), is poorly defined. Here we report the analysis of mice with null mutations of Wrn, Blm, and RecQ1 genes that are related to Mut-7 and Qde3, two genes essential for RNAi in Caenorhabditis elegans and quelling in Neurospora, respectively. Our results suggest that Wrn, Blm, and RecQ1 are not involved in sequence-specific mRNA degradation in mammals in response to dsRNA, suggesting potential differences in the mammalian RNAi pathway.

Adenosine Triphosphatases↗
PubMed2000

Acute toxicity test with Daphnia magna: an alternative to mammals in the prescreening of chemical toxicity?

In this study, the association between the acute toxicity of 15 compounds to Daphnia magna, expressed as 24- and 48-h LC(50) values, and the corresponding oral LD(50) values for the rat was tested. Since there was evidence of a strong relationship between the two species, the sample was extended to 54 cases by including the values for acute toxicity to D. magna and rat of more chemicals published by other authors. Thus, a total of 54 data points were further used to ascertain the relationship between the acute toxicity of chemical compounds to D. magna and that to the rat. To summarize its validity, the D. magna test is more specific than sensitive as an indicator of toxicity to the rat. When it is used with a chemical that has a high probability of being very toxic to D. magna (LC(50)< 0.22 mg/L), the test provides considerable information if it is positive, virtually giving evidence of toxicity to the rat (with a probability of 0.83). On the other hand, a negative test (D. magna LC(50)>0.22 mg/L) has a probability of correctly assigning nontoxicity to the rat equal to 0.74. This study and results published by other authors provide good evidence of the applicability of using invertebrate tests as prescreening methods, thus considerably reducing the number of mammals required in toxicity testing.

Animals↗
PubMed1995

Pharmacological and genetic approaches for the study of circadian rhythms in mammals.

Two different approaches have been utilized to study the controlling mechanisms that underlie the generation and entrainment of circadian rhythms in mammals. The use of specific drugs to alter the period and/or the phase of circadian rhythms has provided new insights into both the pathways by which environmental information reaches the mammalian circadian pacemaker in the suprachiasmatic nuclei (SCN) and the cellular and neurochemical events within the SCN itself which are involved in circadian rhythmicity. A second approach, which seeks to exploit genetic differences in the properties of the circadian system, holds the promise of eventually defining the cellular and molecular events that are part of the clock itself, the events that underlie the entrainment of the circadian clock by environmental factors, and the expression of overt rhythms driven by the clock. It is anticipated that the pharmacological and genetic approaches to the study of circadian rhythms will complement each other as the underlying physiological mechanisms of the circadian clock system become defined.

Afferent Pathways↗

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