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R P Erickson

Publications and source records attributed to R P Erickson.

At least 55 records · Page 3Linked to original sources
PubMed1997

Increased expression of caveolin-1 in heterozygous Niemann-Pick type II human fibroblasts.

Human Niemann-Pick type II fibroblasts, which encompass the panethnic type C (NPC) and Nova Scotia Acadian type D (NPD) variants, exhibit altered expression of caveolin-1 protein when examined by immunoblotting using an anti-caveolin-1 monoclonal antibody. Unexpectedly, caveolin-1 in heterozygous fibroblasts was significantly elevated as much as 10-fold compared to caveolin-1 in normal and homozygous affected fibroblasts. Homozygous NPC fibroblasts expressed caveolin-1 levels similar to those in normal fibroblasts, while the expression of caveolin-1 in homozygous NPD fibroblasts was slightly elevated. Northern analysis indicates that normal fibroblasts and NPC heterozygous fibroblasts have similar amounts of caveolin-1 mRNA, while NPC homozygous fibroblasts have significantly less caveolin-1 mRNA. In contrast, heterozygous and homozygous NPD fibroblasts exhibit increased levels of caveolin-1 mRNA. These novel findings suggest that caveolin-1 containing subcellular structures are involved in the pathophysiology of Niemann-Pick type II disease. Furthermore, altered caveolin-1 protein expression may serve as a useful marker for the diagnosis of carriers of NPC or NPD.

Caveolin 1↗
PubMed1997

Genome scan for teratogen-induced clefting susceptibility loci in the mouse: evidence of both allelic and locus heterogeneity distinguishing cleft lip and cleft palate.

Nonsyndromic clefting of the lip and palate in humans has a highly complex etiology, with both multiple genetic loci and exposure to teratogens influencing susceptibility. Previous studies using mouse models have examined only very small portions of the genome. Here we report the findings of a genome-wide search for susceptibility genes for teratogen-induced clefting in the AXB and BXA set of recombinant inbred mouse strains. We compare results obtained using phenytoin (which induces cleft lip) and 6-aminonicotinamide (which induces cleft palate). We use a new statistical approach based on logistic regression suitable for these categorical data to identify several chromosomal regions as possible locations of clefting susceptibility loci, and we review candidate genes located within each region. Because cleft lip and cleft palate do not frequently co-aggregate in human families and because these structures arise semi-independently during development, these disorders are usually considered to be distinct in etiology. Our data, however, implicate several of the same chromosomal regions for both forms of clefting when teratogen-induced. Furthermore, different parental strain alleles are usually associated with clefting of the lip versus that of the palate (i.e., allelic heterogeneity). Because several other chromosomal regions are associated with only one form of clefting, locus heterogeneity also appears to be involved. Our findings in this mouse model suggest several priority areas for evaluation in human epidemiological studies.

6-Aminonicotinamide↗
PubMed1997

Neural responses to bitter compounds in rats.

To determine whether the idiosyncratic distribution of transduction mechanisms for bitter tastants in rat taste receptor cells (TRCs) could be inferred from the neural activity they evoke, single neuron responses to ten bitter-tasting compounds were recorded from rat glossopharyngeal (n = 30) and chorda tympani (n = 22) neurons. Responses to several 'bitter' alkaloids were obtained: 10 mM quinine-HCl, 50 mM caffeine, and 1 mM each nicotine, yohimbine, and strychnine, plus a number of non-alkaloid bitter-tasting compounds: 0.1 M KCl, 0.01 M MgCl2, and 1 mM each phenylthiocarbamide (PTC), L-tyrosine, and denatonium benzoate. To obtain some distinctions with other stimuli NaCl (0.1 M), HCl (pH 2.0), and capsaicin (10 microM) were also tested. It was found that individual neurons in both glossopharyngeal and chorda tympani nerves differed in their relative sensitivities to the various bitter stimuli. To determine relationships among these stimuli, the differences in the evoked responses between each stimulus pair were summarized in a multi-dimensional scaling space. In these analyses neither nerve showed any obvious similarity between the placements of quinine and the other bitter stimuli. Such data suggest that first-order gustatory neurons can discriminate among the above bitter stimuli. For glossopharyngeal neurons, some similarity to quinine was found only for nicotine and denatonium, and for chorda tympani neurons, some similarity to quinine was found only for KCl and MgCl2. Of the bitter compounds tested, quinine evoked the greatest response from glossopharyngeal neurons. We propose this arises because quinine can activate TRCs by more transduction mechanisms than other bitter stimuli. The results from these studies were summarized in a qualitative model for the coding of bitter tastants where the variety of transduction mechanisms for bitters are distributed among various TRCs to account for the heterogeneous responses among the neurons.

Animals↗
PubMed1997

Does sex determination start at conception?

Recent molecular studies of mammalian sexual determination have been focused on gene expression in the gonadal ridge at the time of appearance of sexual dimorphism: the critical time defined by the 'Jost principle'. Three lines of evidence suggest that, instead, sex determination may start shortly after conception: (1) the XY preimplantation embryo usually develops more rapidly than the XX preimplantation embryo (this phenotype has been linked to the Y chromosome and will be termed 'Growth factor Y'); (2) the gene for testis determination, SRY/Sry, and the closely linked genes ZFY/Zfy and Smcy, are transcribed in the preimplantation embryo; and (3) male and female preimplantation embryos are antigenically distinguishable, indicating sex differences in gene expression. The data to support these assertions are reviewed. Possible relationships of these three phenomena to each other and to sex differentiation are discussed. Similarities in mechanisms of sexual determination between marsupial and eutherian mammals are hypothesized. Problems with interpreting male sexual differentiation as being solely due to testosterone and Müllerian inhibiting substance (MIS) are discussed.

Animals↗
PubMed1997

Molecular and clinical studies of three cases of female pseudohermaphroditism with caudal dysplasia suggest multiple etiologies.

Female pseudohermaphroditism with caudal dysplasia is a clinical entity in which normal-appearing male genitalia may occur in the apparent absence of testosterone or the sex-determining gene (SR Y). We have extended observations of two previously reported cases, and report a third case, which strongly suggests multiple etiologies. The first case was one of identical twins. The other identical twin did not show female pseudohermaphroditism with caudal dysplasia, but both patients had the rare birth defect of neonatal cataracts. We have explored skewed X-inactivation as a possible difference between the two twins, with a negative result. The second case had a deletion at 10q25.3-->ter. This is near the location of PAX2, and we searched for mutations in PAX2 in both this and the first case, with negative results. Neither patient had a scrotal raphe, suggesting that a failure of division of the cloacal membrane was an important step in their development of female pseudohermaphroditism. The final case is newly described and differed from the above two in the presence of a scrotal raphe and an elevated testosterone level. Although no source for the testosterone was found, this case suggests that the etiology in this patient was different and that the presence of a scrotal raphe can be used to distinguish between at least two etiologies.

Abnormalities, Multiple↗
PubMed1996

Molecular analysis in true hermaphrodites with different karyotypes and similar phenotypes.

True hermaphroditism is characterized by the development of ovarian and testicular tissue in the same individual. Müllerian and Wolffian structures are usually present, and external genitalia are often ambiguous. The most frequent karyotype in these patients is 46,XX or various forms of mosaicism, whereas 46,XX is very rarely found. The phenotype in all these subjects is similar. We studied 10 true hermaphrodites. Six of them had a 46,XX chromosomal complement: 3 had been reared as males and 3 as females. The other 4 patients were mosaics: 3 were 46,XX/46,XY and one had a 46,XX/47,XXY karyotype. One of the 46,XX/46,XY mosaics was reared as a female, whereas the other 3 mosaics were reared as males. The sex of assignment in the 10 patients depended only on labio-scrotal differentiation. Molecular studies in 46,XX subjects documented the absence of Y centromeric sequences in all cases, arguing against hidden mosaicism. One patient presented Yp sequences (ZFY+, SRY+), which contrast with South African black 46,XX true hermaphrodites in whom no Y sequences were found. Molecular analysis in the subjects with mosaicism demonstrated the presence of Y centromeric and Yp sequences confirming the presence of a Y chromosome. Gonadal development, endocrine function, and phenotype in the 10 patients did not correlate with the presence of a Y chromosome or Y-derived sequences in the genome, confirming that true hermaphroditism is a heterogeneous condition.

Adolescent↗
PubMed1996

Species variation in the testicular angiotensin converting enzyme promoter studied in transgenic mice.

We have studied the control of transcription of the testicular angiotensin converting enzyme (ACEt) in normal and transgenic mice. Northern analyses, including a developmental curve and separated germ cells, for ACEt mRNA suggest predominantly post-meiotic expression. Mice transgenic for a construct containing the proximal 298 bp of the rabbit ACEt promoter, with chloramphenicol acetyl transferase (CAT) as a recorder, showed correct tissue regulation while a 86 bp fragment of the promoter led to no expression. Many candidate transacting factor binding elements, previously identified as candidate regulators of transcription driving spermatogenesis, are scattered across this 298 bp in the rabbit (but not the mouse) promoter and may lead to tissue specificity. The recent finding that the proximal 91 bp of the mouse ACEt promoter leads to tissue specific expression of a recorder gene (Howard et al., 1993) emphasizes the difference between the two species and the importance of a cAMP response element (CRE) within this fragment for tissue specific expression. This CRE is conserved in the rabbit promoters we used.

Animals↗
PubMed1996

Mouse models of human genetic disease: which mouse is more like a man?

There has always been great interest in animal models of human genetic disease, and mice provide the largest number of examples. A mutation in the homologous gene in mice does not always lead to the same phenotype as is found in man, however. Recent studies made it apparent that one mutation can have markedly different phenotypes when placed on different genetic backgrounds. This variation is due to different alleles at modifying loci in various inbred strains. Thus, if one wishes to obtain the optimal mouse model for a human disease, one needs to choose the correct genetic background as well as the correct mutation.

Alleles↗
PubMed1996

Size of 22q deletions in four previously reported patients with conotruncal anomaly face syndrome.

Conotruncal anomaly face syndrome (CTAFS) was distinguished from velo-cardio-facial syndrome (VCFS) in a bind study, yet shared the finding of 22q11.2 deletions. This work has been extended to show that the 22q11.2 deletions in CTAFS greatly overlap those found in VCFS and many DiGeorge patients. The reason for dissimilar phenotypes with apparently similar 22q11.2 deletions is not yet known.

Abnormalities, Multiple↗
PubMed1995

Sequence variation in the 5', putative promoter of Sry and its possible relevance to the C57BL/6J-YDOM sex reversal.

Sry is the testes determining factor gene located on the Y chromosome. We sought sequence variation in potential promoter regions that might explain the gradiation in sex reversal seen when different domesticus strains are bred to C57BL/6J females since sequence variation previously found in the coding region is not sufficient to explain it. Dideoxy sequencing identified a 10 bp deletion in the 5' flanking region limited to YDOM chromosomes of weak effect. A PCR strategy to search for deletions in this region disclosed another deletion which was shown to be different by sequencing.

Animals↗
PubMed1995

Cloning, sequence analysis, and expression of a mouse cDNA encoding cytochrome c oxidase subunit VIa liver isoform.

A cDNA encoding cytochrome c oxidase (COX) subunit VIa liver isoform (COX6aL) was isolated from a Mus musculus library and sequenced. The protein translated from the nucleotide sequence contains a presequence and is 91% identical to the human cognate sequence over the processed polypeptide region. Northern analysis shows the expression of COX6aL is developmentally regulated in heart, being about equally transcribed with the heart isoform (COX6aH) in 18-day embryos but consisting of less than 25% in adult heart.

Amino Acid Sequence↗
PubMed1995

SRY alone can induce normal male sexual differentiation.

Most individuals with the rare 46,XX male "syndrome" arise due to an unequal interchange between Xp and Yp termini during paternal meiosis. The pattern of Y-sequences in these patients varies considerably, but very few cases have been reported showing only SRY. The phenotype in these patients is also variable ranging from severe impairment of the external genitalia through hypospadias and/or cryptorchidism to occasional normal male phenotype. We report a Mexican 46,XX male patient without genital ambiguities in whom DNA analysis showed the presence of SRY and the absence of ZFY. We conclude that in this case SRY alone was enough for complete male sexual differentiation.

DNA-Binding Proteins↗
PubMed1995

Mutagenesis and human genetic disease: an introduction.

This special issue attempts to provide a fresh perspective on the importance of germ-cell mutagenesis studies and restate the questions and challenges inherent in efforts to minimize the incidence of human genetic diseases. We are working in a time when rapidly advancing molecular technologies provide the tools that permit a more detailed understanding of germ-cell mutagenesis and genetic disease. Meanwhile, discoveries of new genetic disease phenomena challenge our abilities to conceive and develop research models for their study. It is hoped that the collection of articles in this issue will serve to stimulate interest in scientists of varied disciplines and help focus those interests on the issues surrounding the relationship between environmental mutagens and human genetic disease.

Aneuploidy↗
PubMed1995

The new human genetics.

This overview for the special issue of Environmental and Molecular Mutagenesis devoted to recent advances in human genetics relevant to mutagenesis briefly surveys the advances in the field. We present the evidence that trinucleotide repeat expansion can cause anticipation in human inherited disease. The finding that transposons are active in humans, as they are in other organisms, is reviewed. We present an example of two different diseases being caused by mutations in one gene. The role of mitochondrial mutations and parent-specific gene origin effects ("imprinting") are briefly reviewed; fuller reviews are provided in other articles in this special issue. Finally, the relevance of epigenetic inheritance by protein-protein interaction is included.

Animals↗