Biomedical subjects

Molly A Bogue

Publications and source records attributed to Molly A Bogue.

8 recordsLinked to original sources

PubMed2006

Mouse Phenome Database (MPD).

The Mouse Phenome Database (MPD; http://www.jax.org/phenome) is a repository of phenotypic and genotypic data on commonly used and genetically diverse inbred strains of mice. Strain characteristics data are contributed by members of the scientific community. Electronic access to centralized strain data enables biomedical researchers to choose appropriate strains for many systems-based research applications, including physiological studies, drug and toxicology testing and modeling disease processes. MPD provides a community data repository and a platform for data analysis and in silico hypothesis testing. The laboratory mouse is a premier genetic model for understanding human biology and pathology; MPD facilitates research that uses the mouse to identify and determine the function of genes participating in normal and disease pathways.

Animals↗

PubMed2006

Identification of candidate alkylator-induced cancer susceptibility genes by whole genome scanning in mice.

Secondary malignancies are a serious adverse consequence of alkylator chemotherapy. The risk of developing an alkylator-associated malignancy is influenced by genetic background, although the relevant genetic factors are poorly understood. To screen for novel susceptibility factors, we established a mouse model of alkylator-induced malignancy. We exposed mice from 20 inbred strains to the prototypical alkylating agent, N-nitroso-N-ethylurea (ENU). ENU was a potent carcinogen in many of the strains tested, inducing 140 tumors in 240 ENU-treated mice (66% incidence of at least one tumor in evaluable mice), compared with a background incidence of 8% spontaneous tumors in 240 strain-, age-, and sex-matched control mice (relative risk, 8.4; P < 0.0001). A wide variety of tumor histologies were noted, including epithelial carcinomas, soft tissue sarcomas, and hematopoietic tumors. Cancer susceptibility was a heritable trait for the most common tumor types, lung adenocarcinoma (H(2) = 0.25), T cell lymphoma (H(2) = 0.19), and myeloid malignancies (H(2) = 0.10). Quantitative trait locus mapping identified regions on chromosomes 3, 6, 9, and 15 containing candidate genes associated with lung adenoma, lung carcinoma, and lymphoma susceptibility. This novel mouse model recapitulates many features of human alkylator-associated cancer and supports the hypothesis that susceptibility to this syndrome is influenced by inherited polymorphisms that could be used to make informed clinical treatment decisions.

Alkylating Agents↗

PubMed2004

Use of a dense single nucleotide polymorphism map for in silico mapping in the mouse.

Rapid expansion of available data, both phenotypic and genotypic, for multiple strains of mice has enabled the development of new methods to interrogate the mouse genome for functional genetic perturbations. In silico mapping provides an expedient way to associate the natural diversity of phenotypic traits with ancestrally inherited polymorphisms for the purpose of dissecting genetic traits. In mouse, the current single nucleotide polymorphism (SNP) data have lacked the density across the genome and coverage of enough strains to properly achieve this goal. To remedy this, 470,407 allele calls were produced for 10,990 evenly spaced SNP loci across 48 inbred mouse strains. Use of the SNP set with statistical models that considered unique patterns within blocks of three SNPs as an inferred haplotype could successfully map known single gene traits and a cloned quantitative trait gene. Application of this method to high-density lipoprotein and gallstone phenotypes reproduced previously characterized quantitative trait loci (QTL). The inferred haplotype data also facilitates the refinement of QTL regions such that candidate genes can be more easily identified and characterized as shown for adenylate cyclase 7.

Adenylyl Cyclases↗

PubMed2004

A collaborative database of inbred mouse strain characteristics.

UNLABELLED: A database and website (MPD: Mouse Phenome Database) have been developed to serve as a consolidated home for mouse strain characterization data being generated by the scientific community. Physiological, anatomical and behavioral data are being collected and integrated into a common framework for tabulation by strain and sex. Genotypic data are being collected as well. The current focus is on a set of 40 inbred strains. The MPD as of February 2004 contains approximately 500 phenotypic parameters relevant to human health, voluntarily contributed by several dozen investigators and laboratories. AVAILABILITY: www.jax.org/phenome

Animals↗

PubMed2004

The Mouse Phenome Project.

The laboratory mouse is the organism of choice for many studies in biology and medicine. Reliable phenotypic data are essential for the full utility of genotypic information emerging from efforts to sequence human and mouse genomes. The Mouse Phenome Project has been organized to help accomplish this task by establishing a collection of baseline phenotypic data on commonly used and genetically diverse inbred mouse strains and making this information publicly available through a web-accessible database. The Mouse Phenome Database (MPD) is being developed to manage these data and to provide researchers with tools for exploring both raw phenotypic data and comparative summary analyses. The MPD serves as a repository for detailed protocols and raw data. This resource enables investigators to identify appropriate strains for (1) physiological testing, (2) drug discovery, (3) toxicology studies, (4) mutagenesis, (5) modeling human diseases, (6) QTL analyses and identification of new genes and (7) unraveling the influence of environment on genotype.

Animals↗

PubMed2003

Acoustic startle and prepulse inhibition in 40 inbred strains of mice.

A high-throughput phenotype screening protocol was used to measure the acoustic startle response (ASR) and prepulse inhibition (PPI) in mice. ASRs were evoked by noise bursts; prepulses for PPI were 70 dB sound pressure level tones of 4, 12, and 20 kHz. Forty inbred strains of mice were tested (in most cases using 10 males and 10 females of each strain). The data on both the ASR and PPI had high internal and test-retest reliability and showed large differences among inbred strains, indicative of strong genetic influences. Previously obtained measures of hearing sensitivity in the same inbred strains were not significantly correlated with ASR or PPI measures.

Acoustic Stimulation↗

PubMed2003

Invited review: Identifying new mouse models of cardiovascular disease: a review of high-throughput screens of mutagenized and inbred strains.

The mouse is a proven model for studying human disease. Many strains exist that exhibit either natural or engineered genetic variation and thereby enable the elucidation of pathways involved in the development of cardiovascular disease. Although those mouse models have been fundamental to advancing our knowledge base, we are still at an early stage in understanding how genes contribute to complex disorders. There remains a need for new animal models that closely represent human disease. To expedite their development, we have established the Center for New Mouse Models of Heart, Lung, Blood, and Sleep Disorders at The Jackson Laboratory. We are using a phenotype-driven approach to identify mutations leading to atherosclerosis, hypertension, obesity, blood disorders, lung dysfunction, thrombosis, and disordered sleep. Our high-throughput, comprehensive phenotyping draws from two sources for new models: 1) the natural variation among over 40 inbred mouse strains and 2) chemically induced, whole-genome mutagenized mice. Here, we review our cardiovascular screens and present some hypertensive, obese, and cardiovascular models identified with this approach.

Animals↗

PubMed2002

Large-scale, high-throughput screening for coagulation and hematologic phenotypes in mice.

The Mouse Phenome Project is an international effort to systematically gather phenotypic data for a defined set of inbred mouse strains. For such large-scale projects the development of high-throughput screening protocols that allow multiple tests to be performed on a single mouse is essential. Here we report hematologic and coagulation data for more than 30 inbred strains. Complete blood counts were performed using an Advia 120 analyzer. For coagulation testing, we successfully adapted the Dade Behring BCS automated coagulation analyzer for use in mice by lowering sample and reagent volume requirements. Seven automated assay procedures were developed. Small sample volume requirements make it possible to perform multiple tests on a single animal without euthanasia, while reductions in reagent volume requirements reduce costs. The data show that considerable variation in many basic hematological and coagulation parameters exists among the inbred strains. These data, freely available on the World Wide Web, allow investigators to knowledgeably select the most appropriate strain(s) to meet their individual study designs and goals.

Animals↗