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K Figueroa

Publications and source records attributed to K Figueroa.

8 recordsLinked to original sources
PubMed2000

Nuclear localization or inclusion body formation of ataxin-2 are not necessary for SCA2 pathogenesis in mouse or human.

Instability of CAG DNA trinucleotide repeats is the mutational mechanism for several neurodegenerative diseases resulting in the expansion of a polyglutamine (polyQ) tract. Proteins with long polyQ tracts have an increased tendency to aggregate, often as truncated fragments forming ubiquitinated intranuclear inclusion bodies. We examined whether similar features define spinocerebellar ataxia type 2 (SCA2) pathogenesis using cultured cells, human brains and transgenic mouse lines. In SCA2 brains, we found cytoplasmic, but not nuclear, microaggregates. Mice expressing ataxin-2 with Q58 showed progressive functional deficits accompanied by loss of the Purkinje cell dendritic arbor and finally loss of Purkinje cells. Despite similar functional deficits and anatomical changes observed in ataxin-1[Q80] transgenic lines, ataxin-2[Q58] remained cytoplasmic without detectable ubiquitination.

Animals↗
PubMed1998

The mouse SCA2 gene: cDNA sequence, alternative splicing and protein expression.

Spinocerebellar ataxia type 2 (SCA2) is caused by expansion of a CAG trinucleotide repeat located in the coding region of the human SCA2 gene. Sequence analysis revealed that SCA2 is a novel gene of unknown function. In order to provide insights into the molecular mechanisms of pathogenesis of SCA2 and to identify conserved domains, we isolated and characterized the mouse homolog of the SCA2 gene. Sequence and amino acid analysis revealed 89% identity at the nucleotide and 91% identity at the amino acid level. However, there was no extended polyglutamine tract in the mouse SCA2 cDNA, suggesting that the normal function of SCA2 is not dependent on this domain. Northern blot analysis of different mouse tissues indicated that the mouse SCA2 gene was expressed in most tissues, but at varying levels. Alternative splicing seen in human SCA2 was conserved in the mouse. By northern blot analysis, SCA2 was expressed during embryogenesis as early as day 8 of gestation (E8). Immunohistochemical staining using affinity-purified antibodies demonstrated that ataxin 2 was expressed in the cytoplasm of Purkinje cells as well as in other neurons of the CNS.

Alternative Splicing↗
PubMed1997

A high-resolution PAC and BAC map of the SCA2 region.

The spinocerebellar ataxia type 2 (SCA2) gene has been localized to chromosome 12q24.1. To characterize this region and to aid in the identification of the SCA2 gene, we have constructed a 3.9-Mb physical map, which covers markers D12S1328 and D12S1329 known to flank the gene. The map comprises a contig of 84 overlapping yeast artificial chromosomes (YACs), P1 artificial chromosomes (PACs), and bacterial artificial chromosomes (BACs) onto which we placed 82 PCR markers. We localized eight genes and expressed sequence tags on this map, many of which had not been precisely mapped before. In contrast to YACs, which showed a high degree of chimerism and deletions in this region, PACs and BACs were stable. Only 1 in 65 PACs contained a small deletion, and 2 in 18 BACs were chimeric. The high-resolution physical map, which was used in the identification of the SCA2 gene, will be useful for the positional cloning of other disease genes mapped to this region.

Ataxins↗
PubMed1997

A comparison of three-dimensional spiral computed tomoangiography with renal angiography in the live-donor work-up.

The purpose of this study was to investigate the safety and efficacy of three-dimensional spiral computed tomoangiography (3-D spiral CTA) of the abdomen as a substitute for renal angiography in the evaluation of potential live kidney donors. Two of 10 potential live renal donors underwent 3-D spiral CTA only, whereas the remaining 8 underwent 3-D spiral CTA and renal angiography before transplantation. 3-D spiral CTA and renal angiography results were compared and correlated with intraoperative findings. In all 8 cases in which 3-D spiral CTA and renal angiography were compared, the number of arteries was correctly identified by both modalities. In this limited study, 3-D spiral CTA provided the same information as did angiography. According to these findings, 3-D spiral CTA might be used as an alternative to renal angiography, though a larger series is needed to determine whether it could replace renal angiography for all potential live-donor work-ups.

Adult↗
PubMed1996

Identification of three neurofibromatosis type 2 (NF2) gene mutations in vestibular schwannomas.

Vestibular schwannomas (VSs) are common benign tumors of Schwann cell origin and are frequently found in patients with neurofibromatosis type 2 (NF2). We analyzed 15 sporadic VSs for mutations in the tumors, two of which contained loss of heterozygosity (LOH). One of the tumors contained a novel mutation, a 19-bp deletion in exon 4. The two other tumors contained an identical mutation, a complete exon 4 deletion. The exon 4 deletion represents the second most frequently reported mutation of the NF2 gene in VSs.

Chromosome Deletion↗
PubMed1996

Identification of three new microsatellite markers in the spinocerebellar ataxia type 2 (SCA2) region and 1.2 Mb physical map.

Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease recently mapped to chromosome 12q close to the locus D12S84 by genetic linkage analysis. To generate additional genetic markers in the SCA2 region, we constructed a physical map of the region using yeast artificial chomosome (YAC), P1 artificial chromosome (PAC) and cosmid clones. The physical map was found to agree well with the genetic map. Three novel microsatellite markers were isolated and physically mapped. A novel approach to isolate CAG repeats directly from YAC DNAs is described.

Alleles↗
PubMed1994

Mutations of the neurofibromatosis type 2 gene and lack of the gene product in vestibular schwannomas.

Schwannomas are common tumors of the nervous system and are frequently found in patients with neurofibromatosis (NF) 2. Although loss of heterozygosity in NF2 tumors suggests that the NF2 gene functions as a tumor suppressor gene, the NF2 gene shows amino acid sequence homology to structural proteins in one of which dominantly acting mutations have been described. We performed a mutational analysis in 30 vestibular schwannomas and examined the effect of mutations on the NF2 protein. We detected 18 mutations in 30 vestibular schwannomas of which seven contained loss or mutation of both NF2 alleles. Most mutations were predicted to result in a truncated protein. Mutational hot spots were not identified. Immunocytochemical studies using antibodies to the NF2 protein showed complete absence of staining in tumor Schwann cells, whereas staining was observed in normal vestibular nerve. These data indicate that loss of NF2 protein function is a necessary step in schwannoma pathogenesis and that the NF2 gene functions as a recessive tumor suppressor gene.

Amino Acid Sequence↗