This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. DESCRIPTION (provided by applicant): The importance of genetically-engineered mice (GEM) as models of human health and disease has been demonstrated unequivocally. Because of the importance of GEM in biomedical research, the numbers of GEM lines have grown exponentially over the last five years;this astronomical growth is predicted to continue. Recognizing the scientific importance of sharing mice among investigators, the NIH developed a mouse sharing policy which states that mouse lines generated with the aid of NIH funding must be distributed and shared with the scientific community. To accomplish this goal, the NIH funded the establishment of four regional Mutant Mouse Resource and Research Centers (MMRRCs) in 1999 and 2000. This application is a competitive renewal for the Missouri/Harlan (M/H) MMRRC.
Specific Aims of the proposal are: (1) To improve the efficiencies of the MMRRC service functions while continuing to provide the scientific community with a mutant mouse repository and distribution center of the highest quality. To accomplish this, we will employ state-of-the-art cryopreservation and reanimation (reestablishment of lines after cryopreservation) technologies, such as intracytoplasmic sperm injection (ICSI), nuclear transfer (NT) ovarian tissue (OT) transplantation (OTT) and injection of NT derived embryonic stem cells (ntES cells) into tetraploid embryos (ntES/4N). Using these approaches we will be able to more efficiently import, cryopreserve and reanimate lines at a cost approximately 10% of current, traditional embryo cryopreservation based approaches. (2) To conduct research aimed at increasing the value of the MMRRC. Research will include projects aimed at improving assisted reproductive technologies (ARTs) used for reanimation of mouse lines, development of biosensors for detection of pathogens and health surveillance of mutant mouse colonies, and development of new genetic and ARTs that will revolutionize the speed and efficiency with which congenic strains of mice are made. The proposed approach to the operation of the M/H MMRRC represents a new paradigm for mouse repositories. Recognizing the continued exponential growth of GEM, a new paradigm is mandatory;existing mouse resource centers simply cannot archive all of the important mouse lines using traditional methodology. Furthermore, the proposed research projects will result in even greater efficiencies for the MMRRC and the development of new technologies useful to the entire scientific community.

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University of Missouri-Columbia
Veterinary Sciences
Schools of Veterinary Medicine
United States
Zip Code
Benson, James D; Benson, Charles T; Critser, John K (2014) Mathematical model formulation and validation of water and solute transport in whole hamster pancreatic islets. Math Biosci 254:64-75
Kashuba, Corinna M; Benson, James D; Critser, John K (2014) Rationally optimized cryopreservation of multiple mouse embryonic stem cell lines: I--Comparative fundamental cryobiology of multiple mouse embryonic stem cell lines and the implications for embryonic stem cell cryopreservation protocols. Cryobiology 68:166-75
Kashuba, Corinna M; Benson, James D; Critser, John K (2014) Rationally optimized cryopreservation of multiple mouse embryonic stem cell lines: II--Mathematical prediction and experimental validation of optimal cryopreservation protocols. Cryobiology 68:176-84
Rosenfeld, Cheryl S; Sieli, Paizlee T; Warzak, Denise A et al. (2013) Maternal exposure to bisphenol A and genistein has minimal effect on A(vy)/a offspring coat color but favors birth of agouti over nonagouti mice. Proc Natl Acad Sci U S A 110:537-42
Agca, Yuksel (2012) Genome resource banking of biomedically important laboratory animals. Theriogenology 78:1653-65
Benson, James D; Chicone, Carmen C; Critser, John K (2012) Analytical optimal controls for the state constrained addition and removal of cryoprotective agents. Bull Math Biol 74:1516-30
Korampally, Venumadhav; Mamidi, Vamshi Krishna; Harris, Bryant et al. (2011) Sub-minute formation of supported nanoporous mesoscale patterns programmed by surface energy. J Colloid Interface Sci 364:546-54
Benson, James D; Chicone, Carmen C; Critser, John K (2011) A general model for the dynamics of cell volume, global stability, and optimal control. J Math Biol 63:339-59
Hillhouse, Andrew E; Myles, Matthew H; Taylor, Jeremy F et al. (2011) Quantitative trait loci in a bacterially induced model of inflammatory bowel disease. Mamm Genome 22:544-55
Han, Xu; Liu, Yang; Critser, John K (2010) Determination of the quaternary phase diagram of the water-ethylene glycol-sucrose-NaCl system and a comparison between two theoretical methods for synthetic phase diagrams. Cryobiology 61:52-7

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