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P LaPorte

Publications and source records attributed to P LaPorte.

12 recordsLinked to original sources
PubMed2004

Expanded characterization of the social interaction abnormalities in mice lacking Dvl1.

Dvl1 is one of three murine Dishevelled genes widely expressed in embryonic development and in the adult central nervous system. Dishevelled proteins are a necessary component of the Wnt and planar cell polarity developmental signaling pathways. We reported previously that mice deficient in Dvl1 exhibited abnormal social interaction and sensorimotor gating. To assess the validity of our earlier findings, we replicated the previous behavioral tests and included several new assays. The behaviors assessed included: social interaction, sensorimotor reflexes, motor activity, nociception, prepulse inhibition of acoustic startle (PPI) and learning and memory. Assessments with an explicit social component included: social dominance test, whisker trimming, nest building, home-cage huddling and ultrasonic vocalization rate analysis in pups. In addition, separate cohorts of wildtype and Dvl1-null mice were assessed for social recognition of a conspecific. Replicating the original report, Dvl1-null mice were impaired in several tasks containing an explicit social component. However, no impairment was observed in the social memory task. A previously observed deficit in PPI did not replicate in two institutions. In conclusion, we provide evidence that the social interaction phenotype of Dvl1-deficient mice has a strong genetic influence, but the sensorimotor gating deficit was subject to environmental influences. The specificity of observed social interaction deficits also suggests that lack of Dvl1 is associated with deficits in the recognition of social hierarchy and dominance.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Efficient in vivo transduction of the neonatal mouse liver with pseudotyped retroviral vectors.

Ideal methods for human gene therapy will eventually include direct gene transfer to defective tissues in a patient in vivo. Toward that goal, we have used high titer, pseudotyped retroviral vectors expressing genes for the Escherichia coli beta-galactosidase (lacZ) or hepatitis B virus surface antigen (HBsAg) to infect mouse liver by in vivo direct injection into the liver parenchyma. We have found that a single percutaneous injection of small volumes of vectors into the newborn mouse liver leads to transduction of at least 25-30% of the hepatocytes throughout the liver, as judged by in situ staining of liver sections for beta-gal activity at 4 weeks after injection. We have demonstrated that stable levels of HBsAg were also detected in the circulation of injected mice up to 4 months after HBsAg-vector injection. We suggest that the high efficiency of in vivo transduction in the neonatal liver and subsequent stable transgene expression by high-titer pseudotyped retroviral vectors in the absence of an invasive partial hepatectomy may effectively be applied to gene therapy studies in a number of human liver disease [corrected].

Animals↗
PubMed1994

A general method for the generation of high-titer, pantropic retroviral vectors: highly efficient infection of primary hepatocytes.

Retroviral vectors have been central components in many studies leading to human gene therapy. However, the generally low titers and inefficient infectivity of retroviral vectors in human cells have limited their use. We previously reported that the G protein of vesicular stomatitis virus can serve as the exclusive envelope protein component for one specific retroviral vector, LGRNL, that expresses vesicular stomatitis virus G. We now report a more useful general transient transfection scheme for producing very high-titer vesicular stomatitis virus G-enveloped pseudotypes from any Moloney murine leukemia-based retroviral vector without having to rely on the expression of the cytotoxic G protein from the retroviral vector itself. We also demonstrate very high efficiency of infection with a pseudotyped lacZ vector in primary mouse hepatocytes. We suggest that pseudotyped retroviral vectors carrying reporter genes will permit genetic studies in many previously inaccessible vertebrate and invertebrate systems. Furthermore, because these vectors represent retroviral vectors of sufficiently high titer to allow efficient direct retroviral-mediated in vivo gene transfer, we also suggest that pseudotyped vectors carrying potentially therapeutic genes will become useful to test the potential for in vivo gene therapy.

Animals↗
PubMed1993

Provirus-anchored long-range (PAL) mapping of mammalian genomes.

To design a strategy for more efficient long-range physical mapping of large mammalian genomes, we have developed a method for directional mapping from anchor points of randomly integrated retroviral proviruses containing sequences that provide unique cleavage sites in the genome. Using this method, we have determined a physical map of approximately 1.6 Mb flanking an Mo MLV-proviral integration site in mouse NIH/3T3 cells. Our results indicate that this provirus-anchored long-range (PAL) mapping strategy, which uses only two proviral sequences as universal hybridization probes, can potentially allow rapid construction of physical maps for chromosomal regions devoid of other genetic markers.

3T3 Cells↗
PubMed1981

Analysis of transcription of the human Alu family ubiquitous repeating element by eukaryotic RNA polymerase III.

A series of clones that contain human Alu family elements are actively transcribed in soluble in vitro RNA polymerase III systems. The 5' ends of the in vitro transcripts are located about 170 nucleotides upstream of the eponymous Alu I site of the repeat, while a region associated with specifying of the initiation site for in vitro transcription lies in the region between 79 and 106 nucleotides upstream of the central Alu site. Thus, the RNA polymerase III transcription unit defined by the human Alu family is similar to other RNA polymerase III transcription units in possessing an internal region that is required for active transcription in vitro.

Animals↗
PubMed1981

Nucleotide sequence changes in polyoma ts-a mutants: correlation with protein structure.

The mutations in three polyoma ts-a mutants have been determined. Two mutants, ts-25 and ts-52, have different single-base changes at the same position (2883) in the early region corresponding to a conserved glycine residue very near the C-terminus of the polyoma large T antigen. Mutant ts-48 has a single-base change at position 2341, as well as a second change at position 1228, in the region of large T antigen shared with medium T antigen.

Amino Acid Sequence↗
PubMed1979

Regions of the polyoma genome coding for T antigens.

The early region of the polyoma genome encodes three T antigens. We have analyzed the organization of the coding regions for the T antigens, using the nucleotide sequence of polyoma DNA and peptides derived from purified, radio-labeled T antigens, separated by two-dimensional electrophoresis and chromatography. We compared the peptides, predicted from the nucleotide sequence of the DNA, with those derived from the purified T antigens. We also compared chemically synthesized peptides, predicted from the DNA sequence, with observed peptides. The results show that the three polyoma T antigens are encoded in overlapping regions of the viral DNA, translated, in part, in two different reading frames.

Antigens, Viral↗
PubMed1978

Nucleotide sequence studies of polyoma DNA. The Hpa II 3/5 junction to the Hpa II 4/Hae III 18 junction, encoding the origin of DNA replication and the 5' end of the early region.

The nucleotide sequence of polyoma DNA, from near the Hpa II 3/5 unction to the Hpa II 4/ae III 18 junction has been determined by the chemical method of Maxam and Gilbert (Maxam, A., and Gilbert, W. (1977) Proc. Natl. Acad. Sci. U. S. A. 74, 560--564). The sequence contains 878 base paris, including the origin of DNA replication and the region known to encode the hr-t function. The region corresponding to the origin of DNA replication contains several short-repeated sequences and palindromes. There is a 30-base-pair region with striking similarity to the corresponding region of SV40, and, as in SV40, a portion of that sequence is capable of forming a stable hairpin loop. In the region encoding the hr-t function, there is apparently a single open reading frame extending from position 188 to theHpa III 4/Hae III 18 junction. The potential translation product of this open frame begins with an initiation codon starting at position 188, and the first five amino acids of this product are Met-Asp-Arg-Val-Leu. This sequence is similar to the NH2-terminal five amino acids of SV40 small t-antigen known from nucleotide and amino acid sequencing to be Met-Asp-Lys-Val-Leu.

Base Sequence↗