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R P Erickson

Publications and source records attributed to R P Erickson.

At least 91 records · Page 5Linked to original sources
PubMed1993

Developmentally regulated transcription of the four liver-specific genes for inter-alpha-inhibitor family in mouse.

The inter-alpha-inhibitor family is composed of the plasma-protease inhibitors inter-alpha-inhibitor, pre-alpha-inhibitor and bikunin. Inter-alpha-inhibitor and pre-alpha-inhibitor are distinct assemblies of bikunin with distinct sets from three heavy (H) chains designated H1, H2 and H3. These H chains are encoded by a set of three evolutionarily related H genes, and bikunin by an alpha-1-microglobulin/bikunin precursor gene (AMBP). This precursor is cleaved to yield bikunin, a member of the Kunitz-type protease-inhibitor superfamily, and alpha-1-microglobulin, which belongs to the lipocalin superfamily. Northern-blot experiments with RNAs obtained from various tissues in fetal and in adult mice indicated that the transcription of the four AMBP and H genes is liver-restricted, although there is expression of H3 in brain. An analysis of the H1, H2, H3 and AMBP transcripts, as well as of transcripts for other control genes, in liver during development showed a progressive increase in the amounts of the H1, H2, H3 and AMBP RNAs, which all peak transiently at day 5 after birth. This was shown by a nuclear run-on experiment to originate from a change in transcription rate. The transient and postnatal increase in transcription could be explained neither by the liver-restricted expression nor by a common origin of these four genes, nor by a perinatal requirement for many lipocalins or protease inhibitors. This suggests that all four genes are perinatally triggered at the level of similar elements in their transcriptional regulatory regions, a conclusion strengthened by the weak expression of the four genes that is seen in a mutant mouse strain (albino) that is deficient in some liver-specific transcription factors.

Aging↗
PubMed1993

Ion transport across lingual epithelium is modulated by chorda tympani nerve fibers.

Each chorda tympani (CT) nerve innervates taste cells in fungiform papillae on one side of the anterior two-thirds of mammalian tongues. In this study, three effects of unilateral CT transection were investigated: (1) the persistence of taste cells on the ipsilateral and contralateral sides; (2) the ability of the CT to modulate ion transport across the ipsilateral and contralateral sides of canine lingual lingual epithelia; and (3) the effect on contralateral CT responses. Unilateral transection of dog CT caused the mean number of taste buds/fungiform papilla on the ipsilateral side to decrease from five to zero by 29-30 days after surgery. Taste buds reappeared after 44 days but in reduced numbers (two taste buds/papilla). This reappearance of taste buds after 44 days is consistent with the time predicted for the CT to regenerate and reach the anterior portion of the tongue. The number of taste buds/papilla remained unchanged on the contralateral side. Measurements of the short-circuit current (Isc) across both ipsilateral and contralateral sections of isolated canine lingual epithelia were performed at various times after unilateral CT transection. Both sides responded similarly. The Isc began to decline after 3 days, reached a minimum after approximately 18 days (approximately 40% of control Isc) and increased to control values after approximately 40 days. This includes experiments performed 30 days after surgery, when no taste buds were present on the ipsilateral side and the Isc was 80% of control values. For all times after CT transection, amiloride, an epithelial Na+ channel blocker, inhibited Isc. Thus, epithelial cells in dog tongue have amiloride-inhibitable pathways. These results show that proteins involved in active Na+ transport across lingual epithelial can be modulated by CT nerve fibers.

Animals↗
PubMed1993

Transcription of the sex-determining region genes Sry and Zfy in the mouse preimplantation embryo.

We have confirmed the faster growth of male preimplantation mouse embryos. We have also studied the transcription of Y chromosomal genes postulated to have a role in sex determination, using the highly sensitive technique of reverse-transcription polymerase chain reaction at these early stages. We find that two sex-determining region genes, Sry and Zfy, are transcribed during mouse preimplantation development, while the Zfy homologs Zfx and Zfa and a sex-determining region gene originally called A1s9 (now called Ube1y-1) are not. We also show that the anti-Müllerian hormone gene, which contains a Sry consensus binding element in its 5' promoter region, is not transcribed at this time. Developmental curves show that Sry and Zfy are expressed commencing at the two-cell stage. These results suggest that mammalian sex determination starts prior to gonad differentiation.

Animals↗
PubMed1993

Clinical correlates of chromosome 15 deletions and maternal disomy in Prader-Willi syndrome.

We conducted restriction fragment length polymorphism and methylation pattern analyses on 26 typical and atypical patients with Prader-Willi syndrome who did not have a cytogenetically detectable 15q11-13 deletion and on four patients who did have this deletion and were clinically atypical. Maternal disomy for chromosome 15 was identified in 12 patients and paternal deletions in 15q11-13 were found in three cases. Patients with chromosome 15 abnormalities had typical or near typical presentations, based on published diagnostic criteria. Most of the absent criteria in this group were age-dependent features. The remaining 15 patients, including four previously thought to have a cytogenetically apparent 15q11-13 deletion, had neither chromosome 15 molecular abnormality, and these patients were atypical. Patients with maternal disomy had advanced maternal age, suggesting that nondisjunction is part of the etiology of uniparental disomy. This study suggests that molecular diagnosis is critical in patients with Prader-Willi syndrome who appear clinically atypical or who lack a cytogenetically detectable 15q deletion. Methylation pattern analysis is a useful adjunct diagnostic tool for Prader-Willi syndrome.

Adolescent↗
PubMed1993

Creating a conditional mutation of Wnt-1 by antisense transgenesis provides evidence that Wnt-1 is not essential for spermatogenesis.

We have used mice transgenic for an antisense construct for Wnt-1 to study the role of this gene in post-meiotic sperm development. The human PGK-2 promoter provided levels of Wnt-1 antisense mRNA in testes in 5 transgenic lines greatly in excess of Wnt-1 mRNA concentrations, and Wnt-1 mRNA levels were greatly decreased in the lines, by 98% in three of them. There was a general correlation between copy number of the insert, levels of antisense RNA, and decreases in mRNA. There was little effect of the antisense transgene on fertility or testicular histology suggesting that normal levels of Wnt-1 transcript are not essential for spermatogenesis.

Animals↗
PubMed1993

Antisense inhibition of nuclear-encoded cytochrome c oxidase subunits IV and VIIc activity in the pre-implantation embryo.

It had not previously been known whether synthesis of nuclear-encoded mitochondrial subunits occurs in pre-implantation embryos. We have used cytoplasmic injections of antisense RNA transcribed in vitro to study this question. Capped, in vitro transcribed RNA antisense to either cytochrome c oxidase subunit IV or VIIc injected into each cell at the two-cell stage markedly inhibited synthesis of adenine nucleotide by the 8- to 16-cell stage, whereas injection of the cognate sense RNAs gave levels similar to those previously published for normal embryos. These results strongly suggest that translation of nuclear-encoded mRNAs for mitochondrial subunits is required during pre-implantation development. It was of additional interest that, not only was ATP decreased, but ADP and AMP as well, with the effect that the charge ratio remained constant. The results also suggest, therefore, that the mechanism by which cells normally regulate their charge ratio, though to be with adenylate deaminase, is already in place.

Adenosine Diphosphate↗
PubMed1993

Gene expression, X-inactivation, and methylation during spermatogenesis: the case of Zfa, Zfx, and Zfy in mice.

While it has become clear that X-inactivation in the female soma is complete in mouse (in contrast to being "patchy" in man), the degree of X-inactivation in the testes has not been ascertained. We have compared autosomal and X-linked zinc finger homolog expression and X-linked and Y-linked zinc finger homolog methylation in an attempt to elucidate this question. Using RTPCR, we have extended earlier studies of Zfx and Zfa expression in developing testes and find that Zfa expression starts at the time of X-inactivation while Zfx expression is continuous. Cell separation studies did not preclude continued expression of Zfx in adult germ cells. The methylation status of four CCGG residues in the Zfx promoter was studied using PCR bridging this region before and after DNA digestion with the isoschizomers Msp I and Hpa II, the latter being methylation sensitive. Hpa II resistant Zfx promoter DNA was found in all female tissues, but not in male tissues, including the testes. Previous studies have shown that Zfy is expressed at meiosis (like Zfa and unlike Zfx). Despite its expression, the Zfy gene is adjacent to, or contains, highly methylated CCGG sites since hybridization after Msp I digestion detected multiple small fragments that were not released after DNA digestion with Hpa II. Thus, Zfx is not methylated in sperm, while Zfy is, in contrast to their apparent patterns of expression.

Animals↗
PubMed1993

Sites of transcription of the Müllerian inhibiting substance gene in mouse testis.

We have examined the transcription of Müllerian inhibiting substance (MIS) in testis by the sensitive technique of reverse transcription polymerase chain reaction (RTPCR). A developmental study of testis by this nonquantitative technique showed expression at all postnatal stages, including adults while liver and kidney provided negative controls. Cell separation studies indicated that highly purified interstitial cells, as well as less homogeneous Sertoli cell-enriched and germ cell-enriched fractions, contained RNA for MIS. The transcription of MIS in an interstitial cell type was confirmed by finding MIS mRNA in purified Leydig cells. Inasmuch as the germ cell-enriched fraction contains some Sertoli cells, and XX,Sxra and XX,Sxrb which have germ cell-depleted testes, contain MIS mRNA, a Sertoli cell source remains likely for the seminiferous tubule compartment.

Animals↗
PubMed1993

Selectivity of lingual nerve fibers to chemical stimuli.

The cell bodies of the lingual branch of the trigeminal nerve were localized in the trigeminal ganglion using extracellular recordings together with horseradish peroxidase labeling from the tongue. Individual lingual nerve fibers were characterized with regard to their conduction velocities, receptive fields, and response to thermal, mechanical, and chemical stimuli. Fibers were classified as C, A delta, A beta, cold, and warm. The chemical stimuli included NaCl, KCl, NH4Cl, CaCl2, menthol, nicotine, hexanol, and capsaicin. With increasing salt concentration the latency of the response decreased and the activity increased. The responses elicited by salts (to 2.5 M), but not nonpolar stimuli such as menthol, were reversibly inhibited by 3.5 mM of the tight junction blocker, LaCl3. These data suggest that salts diffuse into stratified squamous epithelia through tight junctions in the stratum corneum and stratum granulosum, whereupon they enter the extracellular space. 11 C fibers were identified and 5 were characterized as polymodal nociceptors. All of the C fibers were activated by one or more of the salts NaCl, KCl, or NH4Cl. Three C fibers were activated by nicotine (1 mM), but none were affected by CaCl2 (1 M), menthol (1 mM), or hexanol (50 mM). However, not all C fibers or even the subpopulation of polymodals were activated by the same salts or by nicotine. Thus, it appears that C fibers display differential responsiveness to chemical stimuli. A delta fibers also showed differential sensitivity to chemicals. Of the 35 characterized A delta mechanoreceptors, 8 responded to NaCl, 9 to KCl, 9 to NH4Cl, 0 to CaCl2, menthol, or hexanol, and 2 to nicotine. 8 of 9 of the cold fibers (characterized as A delta's) responded to menthol, none responded to nicotine, 8 of 16 were inhibited by hexanol, 9 of 19 responded to 2.5 M NH4Cl, 5 of 19 responded to 2.5 M KCl, and 1 of 19 responded to 2.5 M NaCl. In summary, lingual nerve fibers exhibit responsiveness to chemicals introduced onto the tongue. The differential responses of these fibers are potentially capable of transmitting information regarding the quality and quantity of chemical stimuli from the tongue to the central nervous system.

Ammonium Chloride↗
PubMed1993

Statistical analysis of neural organization.

1. The responses of 32 taste neurons in the solitary nucleus of the rat to 12 stimuli were analyzed with multidimensional scaling (MDS) and cluster analysis (CA) procedures. These analyses of empirical taste data were compared with similar analyses of two model data sets of known configuration to help clarify the implications of these methods commonly used in forming conclusions about the organization of the taste system. 2. To relate to possible conclusions about groupings in taste, both model data sets were chosen as the best possible examples of ungrouped data, the first being completely regular (in the form of a checkerboard) across the taste space, the second randomly arranged. The analysis of the present empirical data appear to be similar to the present ungrouped models, more so the random than the regular model, in the sense that all are amenable to grouping. 3. Because of the similarity of these model MDS and CA solutions to the present empirical solutions and to most published analyses of this sort, the idea is suggested that the appearance of the plots per se for empirical data does not support the conclusion of grouping. And, technically, MDS and CA do not have the statistical power to provide conclusions about issues of neural organization. 4. MDS and CA analyses have two very powerful roles relating to their ability to disclose the hidden organization of complex data sets; they may lend support for or refute theories about the data sets developed from other considerations, and may help generate theories for further consideration. The question of groupings is only one of many such issues. 5. Because data in the present and other reports are quite adequately accounted by MDS solutions of low dimensionality, it is suggested that their organization is characterized as continuous (i.e., rather than belonging to several disjoint spaces). 6. The use of correlations as distance measures in MDS and CA procedures distorts the spatial solutions, making analysis by visual inspection misleading. For example, using correlations, the true or natural spatial arrangements of data sets are probably less circular or spherical than shown in published MDS solutions. Also they are probably more evenly distributed across the space in the sense that the points are actually more concentrated toward the centers of the spaces; this may have strong influences on interpretations of the general form of the solutions. CA solutions can be influenced in analogous fashion. These problems of distortion of the solutions can be avoided with use of direct, linear estimates of distances. (ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1993

Facts on PAX.

Explore the source record for details and available documents.

Animals↗
PubMed1992

Metabolic studies in a mouse model of hepatorenal tyrosinemia: absence of perinatal abnormalities.

Radiation induced chromosomal deletions at the albino locus in the mouse, lethal when homozygous, cause abnormalities of expression of several unlinked liver specific genes. Recently, the gene encoding FAH was shown to be included in the deletions. Since in humans FAH mutations cause tyrosinemia type I, deletion homozygous mice were suspected of having tyrosinemia. Studies of plasma amino acids did not confirm this suspicion. Also, succinylacetone levels were normal in fetal and newborn livers of deletion homozygotes. The present evidence, therefore, does not support the assumption that the earlier described ultrastructural and enzyme abnormalities in deletion homozygotes are secondary effects of tyrosinemia caused by the deletion of FAH.

Amino Acid Metabolism, Inborn Errors↗
PubMed1992

An amino acid change in the DNA-binding region of Sry, found in Mus musculus domesticus and other species, does not explain C57BL/6J-YDOM sex-reversal.

Sry is the testes determining factor gene located on the Y chromosome. We have performed dideoxy sequencing or restriction enzyme digestion of Sry sequences amplified by PCR from a variety of inbred strains and species of mice. A nonconservative replacement of Thr for Isoleu at position 61 was found in Sry from the Y chromosome of Mus musculus domesticus, Mus spretus, and Mus caroli. We demonstrate that this variation is not sufficient to explain the gradiation in the sex-reversal seen when different domesticus strains are bred to C57BL/6J females.

Animals↗
PubMed1992

The genes for the inter-alpha-inhibitor family share a homologous organization in human and mouse.

Inter-alpha-inhibitor (I alpha I) and related molecules in human are comprised of three evolutionarily related, heavy (H) chains and one light (L) chain, also termed bikunin. The latter originates from a precursor molecule that is cleaved to yield the bikunin and another protein designated alpha-1-microglobulin (A1m). The four H and L chains are encoded by four distinct genes designated H1, H2, H3, and L. The L and H2 genes are localized onto human chromosomes (chr) 9 and 10, respectively, whereas the H1 and H3 genes are tandemly arranged on chr 3. Mouse poly(A)+ RNAs or endonuclease-restricted mouse DNA were analyzed by standard and pulsed-field gel electrophoresis (PFGE) techniques in agarose gels and blot-hybridized with human H1, H2, H3 or L cDNA probes. The variable sized transcripts and unique restriction fragment patterns detected with each probe indicate that four genes, including one common L gene for A1m and bikunin also exist in mouse. The co-migration of H1- and H3-hybridizing fragments on PFGE suggests that the mouse H1 and H3 genes are also tandemly arranged. An Msp I restriction fragment length polymorphism (RFLP) in the mouse L gene (proposed symbol, Intin-4) links this gene to other genes already mapped at mouse Chr 4 near the brown (b) locus, a homologous region to the human chr 9q32-34 band where the human I alpha I L gene is located. Therefore, a similar number and arrangement of I alpha I genes is found in mouse and human, including the triplication of an H gene ancestor. These results point to an ancient origin of this complex set of genes.

Alpha-Globulins↗
PubMed1992

A potential animal model for studying CF heterozygote advantage: genetic variation in theophylline-inducible colonic chloride currents among inbred strains of mice.

We have used Ussing chambers to measure chloride secretion by colonic segments (mucosa, muscularis, and serosa) from various inbred strains of mice. We found lower theophylline-induced Cl- secretion in the DBA/2J than in the C57BL/6J strain. Their F1 showed significantly higher levels of Cl- secretion than did the C57BL/6J parental strain while colonic segments from five recombinant inbred B x D lines ranged between the C57BL/6J and F1 values. No major component of the variation appeared to be associated with alleles of the met oncogene region of chromosome 6 or the H-2 region of chromosome 17.

Animals↗
PubMed1992

Injection of Antisense RNA specific for E-cadherin demonstrates that E-cadherin facilitates compaction, the first differentiative step of the mammalian embryo.

We have investigated the effect of antisense E-cadherin RNA in the preimplantation mouse embryo. Antisense RNA was injected into each cell of two-cell embryos that were cultured for 2 days until the normal time of compaction and scored for abnormalities. Embryos injected with the antisense RNA showed delayed compaction compared to the embryos injected with control, or sense, RNA. Delayed cleavage was not the cause because nuclear staining with Hoechst dye 33258 showed about the same number of nuclei in both uncompacted embryos injected with antisense RNA compared with compacted embryos injected with sense RNA at the same hours post human chorionic gonadotropin (hCG). Immunofluorescence with a monoclonal antibody to E-cadherin was markedly diminished in embryos injected with antisense RNA compared with control, injected embryos, suggesting that the observed delayed compaction is due to the inhibition of E-cadherin gene expression by antisense RNA. Embryos injected with antisense RNA eventually compacted and then expressed E-cadherin, but at lower apparent levels than controls. Injection of a single blastomere at the two-cell stage created half-embryo abnormalities.

Animals↗
PubMed1992

Trisomy 15 with loss of the paternal 15 as a cause of Prader-Willi syndrome due to maternal disomy.

Uniparental disomy has recently been recognized to cause human disorders, including Prader-Willi syndrome (PWS). We describe a particularly instructive case which raises important issues concerning the mechanisms producing uniparental disomy and whose evaluation provides evidence that trisomy may precede uniparental disomy in a fetus. Chorionic villus sampling performed for advanced maternal age revealed trisomy 15 in all direct and cultured cells, though the fetus appeared normal. Chromosome analysis of amniocytes obtained at 15 wk was normal in over 100 cells studied. The child was hypotonic at birth, and high-resolution banding failed to reveal the deletion of 15q11-13, a deletion which is found in 50%-70% of patients with PWS. Over time, typical features of PWS developed. Molecular genetic analysis using probes for chromosome 15 revealed maternal disomy. Maternal nondisjunction with fertilization of a disomic egg by a normal sperm, followed by loss of the paternal 15, is a likely cause of confined placental mosaicism and uniparental disomy in this case of PWS, and advanced maternal age may be a predisposing factor.

Adult↗