Genes on the distal portion of mouse Chr 11 are also found on human Chr 17. This extreme linkage conservation allows us to utilize the physiologic, pathologic, and molecular similarities of mouse and human in studies that exploit the experimental genetic advantages of the mouse. The primary goal of the proposed research is to obtain new mutations that reflect single gene function on the distal region of mouse Chr 11. Establishing genotype/phenotype in a specific region by mutagenesis can provide a cost effective approach to determining gene function, particularly in gene rich regions. The conserved synteny between mouse and human will provide a direct link to predications of gene function in humans. We will enhance the genetic analysis of mouse Chromosome 11 by inducing mutations with the chemical mutagen N-ethyl-N-nitrosourea. Appropriate genetic markers will be used to isolate recessive embryo and juvenile lethal and visible phenotypes in the second generation (G/2) animals. We will extend the mutational analysis by screening for multiple medically relevant recessive phenotypes that include: a) neurological, behavioral, and sensory organ defects, b) hematopoietic defects, c) autoimmune disease, d) obesity, e) infertility, and f) morphological abnormalities. Homozygous recessive embryos lethal phenotypes will be classified to a particular stage of embryonic death to understand unique aspects of mammalian development. Selected new mutations will be mapped to a higher resolution using deletion sub-intervals and complementation analysis. Some pairwise complementation tests will be performed on mutations like phenotypic classes. We will identify the genes involve din selected mutations, and correlate the molecular lesion with the biological phenotype. Mutations will be provided to the community and availability will be posted on the World Wide Web. Mutant mouse stocks will be frozen as embryos and/or sperm for archival purposes. Our work will generate many new models of human diseases, to help treat and understand diverse disorders such as behavioral maladies, birth defects, infertility, aging, and obesity that will be useful to members of the biomedical community.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
1P01CA075719-01A1
Application #
6269885
Study Section
Project Start
1998-07-15
Project End
1999-04-30
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Type
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030
Hentges, Kathryn E; Pollock, David D; Liu, Bin et al. (2007) Regional variation in the density of essential genes in mice. PLoS Genet 3:e72
Goldman, Alica M; Potocki, Lorraine; Walz, Katherina et al. (2006) Epilepsy and chromosomal rearrangements in Smith-Magenis Syndrome [del(17)(p11.2p11.2)]. J Child Neurol 21:93-8
Lorenzetti, Diego; Antalffy, Barbara; Vogel, Hannes et al. (2004) The neurological mutant quaking(viable) is Parkin deficient. Mamm Genome 15:210-7
Clark, Amander T; Firozi, Karen; Justice, Monica J (2004) Mutations in a novel locus on mouse chromosome 11 resulting in male infertility associated with defects in microtubule assembly and sperm tail function. Biol Reprod 70:1317-24
Walz, Katherina; Spencer, Corinne; Kaasik, Krista et al. (2004) Behavioral characterization of mouse models for Smith-Magenis syndrome and dup(17)(p11.2p11.2). Hum Mol Genet 13:367-78
Yan, Jiong; Keener, Victoria W; Bi, Weimin et al. (2004) Reduced penetrance of craniofacial anomalies as a function of deletion size and genetic background in a chromosome engineered partial mouse model for Smith-Magenis syndrome. Hum Mol Genet 13:2613-24
Hentges, Kathryn E; Justice, Monica J (2004) Checks and balancers: balancer chromosomes to facilitate genome annotation. Trends Genet 20:252-9
Yan, Jiong; Walz, Katherina; Nakamura, Hisashi et al. (2003) COP9 signalosome subunit 3 is essential for maintenance of cell proliferation in the mouse embryonic epiblast. Mol Cell Biol 23:6798-808
Walz, Katherina; Caratini-Rivera, Sandra; Bi, Weimin et al. (2003) Modeling del(17)(p11.2p11.2) and dup(17)(p11.2p11.2) contiguous gene syndromes by chromosome engineering in mice: phenotypic consequences of gene dosage imbalance. Mol Cell Biol 23:3646-55
Kile, Benjamin T; Mason-Garrison, Cammy L; Justice, Monica J (2003) Sex and strain-related differences in the peripheral blood cell values of inbred mouse strains. Mamm Genome 14:81-5

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