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P E Neumann

Publications and source records attributed to P E Neumann.

At least 55 records · Page 3Linked to original sources
PubMed1992

Confirmation of the influence of a chromosome 7 locus on susceptibility to audiogenic seizures.

Mouse strain differences in susceptibility to audiogenic seizures (AGS) are due to allelic differences at multiple genetic loci. Three loci that influence susceptibility to AGS have been mapped on Chromosomes (Chr) 12, 4, and 7 (Asp-1, Asp-2, and Asp-3, respectively). Here we report evidence that confirms linkage of Asp-3 to c on Chr 7 and parental effects on AGS susceptibility, but not genomic imprinting of Asp-3.

Acoustic Stimulation↗
PubMed1992

Inference in linkage analysis of multifactorial traits using recombinant inbred strains of mice.

Recombinant inbred strains have been shown to be important tools for segregation and linkage analysis of multifactorial traits. Tests of association have been used as robust methods of linkage detection, however, guidelines for forming inferences from significance levels have not been generally available. In this paper, lessons learned from a Bayesian statistical approach to linkage analysis of Mendelian traits have been applied to studies of multifactorial traits. Criteria for detection of linkage based on Bonferroni's correction for multiple testing are also discussed.

Animals↗
PubMed1992

ELISA quantitation of dystrophin for the diagnosis of Duchenne and Becker muscular dystrophies.

Duchenne muscular dystrophy patients express little or no dystrophin, while patients with the milder Becker variant produce dystrophin of altered size or quantity. Dystrophin is currently evaluated on Western blots, but quantitation is difficult and the procedure is not available in most clinical laboratories. We describe an enzyme-linked immunosorbent assay (ELISA) for dystrophin that utilizes a carboxyl-terminal capture antibody, and detection antibodies spanning 65% of the molecule. This configuration is selective for dystrophin and reduces the potential for false diagnosis due to loss of antigenic determinants by deletion or the presence of truncated products resulting from frame-shift mutations. The dystrophin ELISA distinguishes Duchenne muscular dystrophy patients from those with unrelated disorders and may have prognostic value for patients with Becker dystrophy. This assay should prove to be an accessible and rapid tool for the diagnosis of Duchenne/Becker muscular dystrophies and for evaluating therapies that attempt to introduce dystrophin or augment its expression.

Antibodies↗
PubMed1991

Swaying is a mutant allele of the proto-oncogene Wnt-1.

Mice homozygous for the recessive mutation swaying (sw) are characterized by ataxia and hypertonia, attributed to the malformation of anterior regions of the cerebellum. We show that sw is a deletion of a single base pair from the proto-oncogene Wnt-1. The deletion is predicted to cause premature termination of translation, eliminating the carboxy-terminal half of the Wnt-1 protein. Histological examination shows that sw is phenotypically identical to a previously described wnt-1 mutation introduced into mice by gene targeting. Although both mutations in Wnt-1 disrupt primarily the development of the anterior cerebellum, they also exhibit a variability in expressivity such that rostrally adjacent structures in the midbrain and caudally adjacent structures in the posterior cerebellum can also be affected.

Alleles↗
PubMed1991

Genetic dissection of susceptibility to audiogenic seizures in inbred mice.

Mice of some inbred strains, such as 21-day-old DBA/2J mice, have generalized convulsions when exposed to intense auditory stimulation. Analysis of susceptibility to audiogenic seizures in BXD recombinant inbred strains has demonstrated the influence of at least three loci. One locus, Asp-1, is located on chromosome 12 between Ah and D12Nyu1; another locus, Asp-2, is on chromosome 4, tightly linked to b. Here we report evidence that Asp-2 is located within an 8-centimorgan segment distal to b and that Asp-3 is linked to Mtv-1 on chromosome 7. We also present evidence that these three loci account for most of the heritable variation in susceptibility to audiogenic seizures in crosses of DBA/2J and C57BL/6J mice and that susceptibility to audiogenic seizures is influenced by genomic imprinting. Thus, genomic imprinting may complicate linkage and mapping studies and should be considered in analyses of complex modes of inheritance.

Animals↗
PubMed1991

Three-locus linkage analysis using recombinant inbred strains and Bayes' theorem.

Recombinant inbred (RI) strains are useful in linkage analysis and gene mapping. However, the generally small number of strains in an RI strain set limits the power of RI strains in linkage detection. Several methods for increasing the power of RI strains have been used, including summing data across RI strain sets and excluding linkage to genomic regions. In this paper, Bayesian analysis is applied to three-locus linkage data. This method further increases the power of RI strains to detect linkage and gives estimations of the probability of each of the three possible gene orders if the test locus is linked to the pair of marker loci. Several examples are presented, including reconsideration of the position of the proto-oncogene L-myc on the mouse linkage map.

Animals↗
PubMed1990

Identification and mapping of a mouse gene influencing cerebellar folial pattern.

Little is known about the role of inheritance in the pattern of cerebral and cerebellar cortical folding, or the causes of individual variation. Inouye and Oda (J. Comp. Neurol., 190 (1980) 357-362) found that the cerebellar folial pattern varies markedly between inbred strains of mice and between individuals in a closed (non-inbred) colony, but shows little variation between individuals within a given inbred strain. They concluded that strain-specific variation in cerebellar folial pattern is under genetic control. In the present study, the folial pattern was examined in crosses between the C57BL/6J and DBA/2J inbred strains of mice, which differ in the presence or absence of a single cerebellar fissure, and in recombinant inbred strains derived from a cross between the same strains. We found that variation is discrete, that neither phenotype is dominant, and that the strain difference is due predominantly to allelic differences at a single locus (Cfp-1) on chromosome 4. Incomplete penetrance of the simpler pattern suggests that this genetic locus interacts in a probabilistic manner with epigenetic mechanisms involved in morphogenesis of the cerebellum.

Animals↗
PubMed1990

Mapping of two genes that influence susceptibility to audiogenic seizures in crosses of C57BL/6J and DBA/2J mice.

The difference in susceptibility to audiogenic seizures (AGS) between C57BL/6J and DBA/2J inbred strains of mice is due to multiple genetic factors. AGS susceptibility was tested in 21-day-old mice from classical crosses, BXD recombinant inbred (RI) strains, a congenic DBA/2N.B6N-Ahb inbred strain and crosses between the BXD RI strains and DBA/2J. Analysis of these data reveals that the variation in AGS susceptibility between these two strains results from allelic differences at three or more loci. Most of the variation is due to allelic differences at two loci. The first, Asp-1 (formerly Ias), is a major gene located on chromosome 12, between Ah and D12 Nyul. The second, Asp-2 (formerly asp), is a minor gene located on chromosome 4, tightly linked to b. The negative correlation of brain stem Ca2(+)-ATPase activity and AGS susceptibility in the BXD RI strains suggests that the strain difference in Ca2(+)-ATPase activity is inherited as a polygenic trait and that Asp-1 and Asp-2 are linked to, or identical to, factors that influence Ca2(+)-ATPase activity.

Acoustic Stimulation↗
PubMed1990

Analysis of the hotfoot (ho) locus by creation of an insertional mutation in a transgenic mouse.

Hotfoot (ho) mutation is a recessive trait in mice, characterized by motor disorder and male sterility, that maps to chromosome 6. We have identified a transgenic mouse pedigree with a similar trait. Using genetic and molecular approaches, we have demonstrated that the foreign DNA element is located in or near the ho locus. This new allele, designated hoJwg and presumably created by insertional mutagenesis, should make it possible to clone the ho gene. Male infertility in hoJwg male homozygotes was determined to be due to inability of sperm to penetrate the zona pellucida. This was demonstrated by rescuing mutant males by a new technique of gamete micromanipulation, zona pellucida drilling. These findings show that zona drilling is useful both for analysis and preservation of animals with reduced male fertility.

Animals↗
PubMed1990

Neuropathological changes in transgenic mice carrying copies of a transcriptionally activated Mos protooncogene.

Independent transgenic mouse lines carrying the mouse Mos protooncogene linked to a retroviral transcriptional control sequence display behavioral abnormalities including circling, head tilting, and head bobbing. This dominant phenotype shows various degrees of penetrance in different transgenic founder animals and lines. Neuronal and axonal degeneration, gliosis, and inflammatory infiltrates are found in all transgenic mouse lines in which behavioral traits are present. Recordings of auditory-evoked potentials in mice of one of these lines demonstrate that transgenic mice are deaf; in these mice spiral ganglia degenerate and most of the cochlear hair cells are absent. By using an S1 nuclease protection assay, we have detected RNA expression of the transgene in all tissues examined and, in particular, at high levels in brain. In situ hybridization experiments show that Mos expression can be detected in specific areas of the central nervous system. Lesions are present in areas with demonstrable overexpression of Mos.

Animals↗
PubMed1990

Construction of the physical map for three loci in chromosome band 13q14: comparison to the genetic map.

Pulsed-field gel electrophoresis (PFGE) and deletion mapping are being used to construct a physical map of the long arm of human chromosome 13. The present study reports a 2700-kilobase (kb) Not I long-range restriction map encompassing the 13q14-specific loci D13S10, D13S21, and D13S22, which are detected by the cloned DNA markers p7D2, pG24E2.4, and pG14E1.9, respectively. Analysis of a panel of seven cell lines that showed differential methylation at a Not I site between D13S10 and D13S21 proved physical linkage of the two loci to the same 875-kb Not I fragment. D13S22 mapped to a different Not I fragment, precluding the possibility that D13S22 is located between D13S10 and D13S21. PFGE analysis of Not I partial digests placed the 1850-kb Not I fragment containing D13S22 immediately adjacent to the 875-kb fragment containing the other two loci. The proximal rearrangement breakpoint in a cell line carrying a del13(q14.1q21.2) was detected by D13S21 but not by D13S10, demonstrating that D13S21 lies proximal to D13S10. Quantitative analysis of hybridization signals of the three DNA probes to DNA from the same cell line indicated that only D13S10 was deleted, establishing the order of these loci to be cen-D13S22-D13S21-D13S10-tel. Surprisingly, this order was estimated to be 35,000 times less likely than that favored by genetic linkage analysis.

Blotting, Southern↗
PubMed1990

Two-locus linkage analysis using recombinant inbred strains and Bayes' theorem.

Recombinant inbred (RI) strains are useful in linkage analysis and gene mapping. The currently available statistical tests of linkage using data derived from the study of RI strains, including a previous Bayesian analysis, have not been stringent enough guides for conclusions about linkage. In this paper, the probability of linkage was estimated using Bayes' theorem. Tables are presented that give the probability of linkage in sets of up to 30 RI strains and the critical values of i (the number of recombinants) in sets of up to 100 RI strains. Several means of increasing the power of RI strains in linkage analysis are discussed.

Animals↗
PubMed1990

[Periodontal atrophy and further findings in aging people].

In a group of 100 patients cared for in a dispensairy system ranging in age from 50 to 59 years with a total of 2122 teeth the following was found: 767 teeth with periodontal atrophy at the vestibulary side, 415 teeth with untreated defects of dental hard tissues in the region of the cemento-enamel-junction, 168 crowns, fillings and/or dental caries. Periodontal atrophy was not the cause of tooth loss; the treatment of secondary lesions could be a problem. As far as the possible etiological factors are concerned especially the exogenous factor toothbrushing could be influenced. An effective brushing technique is recommended.

Aged↗
PubMed1989

Insertional mutation in a transgenic mouse allelic with Purkinje cell degeneration.

Purkinje cell degeneration (pcd) is an autosomal recessive mutation which maps to chromosome 13 in the mouse. The pcd mutation causes loss of cerebellar Purkinje cells, retinal photoreceptor cells, and olfactory bulb mitral cells, as well as abnormalities of spermatogenesis. pcd is among a number of autosomal recessive mutations in mice and humans that affect neurologic function and male fertility. The cloning of one or more of these loci would contribute significantly to our understanding of the genetic control of development and maintenance of affected cell types. We report here identification of a transgenic mouse line with an insertional mutation that is allelic with pcd and manifests histopathologic features indistinguishable from those of the spontaneous mutation. The creation of an allele of pcd by transgene insertion should make possible the cloning of the pcd locus.

Alleles↗