Dr. Johnson's laboratory analyzes the molecular and functional consequences of induced germline mutations on obvious and subtle whole-organism phenotypes in the mouse.

The primary focus for the laboratory of Dr. Dabney K. Johnson is on the molecular and functional analysis of germ-line mutations and complex phenotypes generated by our phenotype-based mouse mutagenesis core program. Our studies are designed to pair specific genes with mutant phenotypes. We develop and employ screening assays to detect behavioral, biochemical, and morphological mutations in mice, and then clone, characterize, and manipulate genes associated with mutant phenotypes that alter function at the organismal level. Students and other investigators perform detailed analysis of the functional consequences of DNA alterations in individual gene sequences, and on how those mutations impact entire biological pathways over the lifespan of the animal. Our mutagenesis and phenotype-screening efforts currently are targeted at mouse chromosome 7, with concentration in specific genome regions covered by complexes of radiation-induced deletions and other chromosomal aberrations. Positional cloning of genes within these chr 7 regions is facilitated by use of deletions to map both mutant phenotypes and DNA markers to minimal intervals for physical mapping and DNA sequencing for gene discovery.

• Dhar, M.S., Sommardahl, C.S., Kirkland, T., Nelson, S., Donnell R., Johnson, D.K., and Castellani, L.W. Mice Heterozygous for Atp10c, a Putative Amphipath, Represent a Novel Model of Obesity and Type 2 Diabetes. J. Nutr. 134: 799-805, 2004 .
• Wu, M. Michaud, E.J., and Johnson, D.K. Cloning and functional study, and comparative mapping of Luzp2 to mouse chromosome 7 and human chromosome 11p13p14. Mamm. Genome 14: 323-334, 2003.
• Johnson, D.K. Phenotype- and gene-driven approaches to discovering the functions of mammalian genes. J. Nutrit. 133: 4269-4270, 2003.
• Rinchik, E. M., D. A. Carpenter, & D. K. Johnson. Functional annotation of mammalian genomic DNA sequence by chemical mutagenesis: a fine-structure genetic mutation map of a 1- to 2-cM segment of mouse chromosome 7 corresponding to human chromosome 11p14-p15. Proc. Natl. Acad. Sci USA, 99: 844-849, 2002.
• Dhar, M. S., Hauser, L., West, D. B., and D. K. Johnson. Genomic structure of a murine aminophospholipid translocase mapping to quantitative trait loci influencing body fat and associated with type 2 diabetes phenotype, Obes. Res. 10: 695-702, 2002.
• Nadeau, J.H., Balling, R., Barsh, G., Beier, D., Brown, S.D.M., Bucan, M, Camper, S., Carlson, G., Copeland, N., Eppig, J., Fletcher, C., Frankel, W.N., Ganten, D., Goldowitz, D., Goodnow. C., Guenet, J.-L., Hicks, G., Hrabe del Angelis, M., Jackson, I., Jacob, H.J., Jenkins, N., Johnson, D., Justice, M., Kay, S., Kingsley, D., Lehrach, H., Magnuson, T., Meisler, M., Poustka, A., Rinchik, E.M., Rossant, J., Russell, L.B., Schimenti, J., Shiroishi, T., Skarnes, W.C., Soriano, P., Stanford, W., Takahashi, J.D., Wurst, W., and Zimmer, A. Functional Annotation of Mouse Genome Sequences. Science, 291: 1251-1255, 2001.
• Sommardahl, C., Cottrell, M., Wilkinson, J.E., Woychik, R.P., and Johnson, D.K. Phenotypic variations of orpk mutation and chromosomal localization of modifiers influencing kidney phenotype. Physiol. Genomics 7: 127-134, 2001.
• Simpson, E.H., Suffolk, R., Bell, J.A., Johnson, D.K., Hunsicker, PR., Justice, M.J., and Jackson, I.J. A comparative transcript map of the Tryp1 (brown) deletion complex homologous to human 9p21-23. Mamm. Genome 11: 58-63, 2000.
• Aponte, J.L., Sega, G.A., Hauser, L.J., Dhar, M.S., Withrow, C.M., Carpenter, D.A., Rinchik, E.M., Culiat, C.T. and Johnson, D.K. Point mutations in the murine fumarylacetoacetate hydrolase gene: Animal models for the human genetic disorder hereditary tyrosinemia type 1, Proc. Natl. Acad Sci, USA, 98: 641-645, 2000.
• Russell, L.B., Hunsicker, P.R., Kerley, M.K., Johnson, D.K., and Shelby, M.D. Bleomycin, unlike other male-mouse mutagens, is most effective in spermatogonia, inducing primary deletions. Mutation Res. 469: 95-105, 2000.
• Wu, Min, Rinchik, E.M., and Johnson, D. K. An integrated deletion and physical map encompassing l71Rl, a chromosome 7 locus required for peri-implantation survival in the mouse. Genomics, 67: 228-231, 2000.
• Dhar, M. S., Webb, L. S., Smith, L., Hauser, L., Johnson, D., and West, D.B. A novel ATPase on mouse chromosome 7 is a candidate gene for increased body fat. Physiological Genomics, 4: 93-100, 2000.
• Simpson, E.H., Suffolk, R., Bell, J.A., Johnson, D.K., Hunsicker, PR., Justice, M.J., and Jackson, I.J. A comparative transcript map of the Tryp1 (brown) deletion complex homologous to human 9p21-23. Mamm. Genome 11: 58-63, 2000.
• Aponte, J.L., Sega, G.A., Hauser, L.J., Dhar, M.S., Withrow, C.M., Carpenter, D.A., Rinchik, E.M.,Culiat, C.T. and Johnson, D.K. Point mutations in the murine fumarylacetoacetate hydrolase gene: Animal models for the human genetic disorder hereditary tyrosinemia type 1, Proc. Natl. Acad Sci, USA, 98: 641-645, 2000.
• Johnson, Dabney K., Carpenter, Donald A., Culiat, Cymbeline T., Goss, Karen A., Klebig, Mitchell L., Michaud, Edward J., Miller, Darla R., Russell, Liane B., You, Yun, and Rinchik, Eugene M. A phenotype-driven approach to the molecular and functional analysis of the mouse genome. In Microbial Status and Genetic Evaluation of Mice and Rats, Proceedings of the 1999 US/Japan meeting, National Research Council, Washington DC, pp. 105-115, 2000.
• Russell, L.B., Hunsicker, P.R., Kerley, M.K., Johnson, D.K., and Shelby, M.D. Bleomycin, unlike other male-mouse mutagens, is most effective in spermatogonia, inducing primary deletions. Mutation Res. 469: 95-105, 2000.
• Wu, Min, Rinchik, E.M., and Johnson, D. K. An integrated deletion and physical map encompassing l71Rl, a chromosome 7 locus required for peri-implantation survival in the mouse. Genomics, 67: 228-231, 2000.
• Dhar, M. S., Webb, L. S., Smith, L., Hauser, L., Johnson, D., and West, D.B. A novel ATPase on mouse chromosome 7 is a candidate gene for increased body fat. Physiological Genomics, 4: 93-100, 2000.
• Johnson, Dabney K., Carpenter, Donald A., Culiat, Cymbeline T., Goss, Karen A., Klebig, Mitchell L., Michaud, Edward J., Miller, Darla R., Russell, Liane B., You, Yun, and Rinchik, Eugene M. A phenotype-driven approach to the molecular and functional analysis of the mouse genome. Invited article for the Proceedings of the 1999 US/Japan meeting, National Research Council, Washington DC, in press.
• Ji, Yonggang, Walkowicz, Mitchell J., Buiting, Karin, Johnson, Dabney K., Tarvin, Rocio E., Rinchik, Eugene M., Horstemke, Bernhard, Stubbs, Lisa J., and Nicholls, Robert D. The ancestral Prader-Willi/Angelman syndrome deletion breakpoint gene encodes a giant protein implicated in protein trafficking and is mutated in jdf2 mice with neuromuscular and spermiogenic abnormalities. Hum. Mol. Gen. 8: 533-542, 1999.
• Vogel, Stefanie N., Johnson, Dabney , Perera, Pin-Yu, Medvedev, Andrei, Larivière, Line, Qureshi, Salman T., and Malo, Danielle. Cutting edge: Functional characterization of the effect of the C3H/HeJ defect in mice that lack an Lpsn gene: In vivo evidence for a dominant negative mutation. J. Immunol. 162: 5666-5670, 1999.
• Walkowicz, M., Ji. Y., Ren, X., Horsthemke, B., Russell, L.B., Johnson, D., Rinchik, E.M., Nicholls, R.D., and Stubbs, L. Molecular characterization of radiation- and chemically induced mutations associated with neuromuscular tremors, runting, juvenile lethality, and sperm defects in jdf2 mice. Mamm. Genome 10: 870-878, 1999.
• Simpson, E.H., Johnson, D.K., Hunsicker, P.R., Suffolk, R., Jordan, S.A., and Jackson, I.J. The mouse Cer1 (Cerberus related or homologue) gene is not required for anterior pattern formation. Devel. Biol. 213: 202-206, 1999.
• Schultze, A.E., McEntee, M F., Daniel, G. B., and Johnson, D.K. Radiographic, histologic, and cytologic lesions associated with mutations in the fitness14226SB locus of mice. Lab. Anim. Sci. 49: 260-268, 1999.
• Ji, Yonggang, Walkowicz, Mitchell J., Buiting, Karin, Johnson, Dabney K., Tarvin, Rocio E., Rinchik, Eugene M., Horstemke, Bernhard, Stubbs, Lisa J., and Nicholls, Robert D. The ancestral Prader-Willi/Angelman syndrome deletion breakpoint gene encodes a giant protein implicated in protein trafficking and is mutated in jdf2 mice with neuromuscular and spermiogenic abnormalities. Hum. Mol. Gen. 8: 533-542, 1999.
• Vogel, Stefanie N., Johnson, Dabney , Perera, Pin-Yu, Medvedev, Andrei, Larivière, Line, Qureshi, Salman T., and Malo, Danielle. Cutting edge: Functional characterization of the effect of the C3H/HeJ defect in mice that lack an Lpsn gene: In vivo evidence for a dominant negative mutation. J. Immunol. 162: 5666-5670, 1999.
• Walkowicz, M., Ji. Y., Ren, X., Horsthemke, B., Russell,L.B., Johnson, D., Rinchik, E.M., Nicholls, R.D., and Stubbs, L. Molecular characterization of radiation- and chemically induced mutations associated with neuromuscular tremors, runting, juvenile lethality, and sperm defects in jdf2 mice. Mamm. Genome 10: 870-878, 1999.
• Simpson, E.H., Johnson, D.K., Hunsicker, P.R., Suffolk, R., Jordan, S.A., and Jackson, I.J. The mouse Cer1 (Cerberus related or homologue) gene is not required for anterior pattern formation. Devel. Biol. 213: 202-206, 1999.
• Schultze, A.E., McEntee, M F., Daniel, G. B., and Johnson, D.K. Radiographic, histologic, and cytologic lesions associated with mutations in the fitness14226SB locus of mice. Lab. Anim. Sci. 49: 260-268, 1999.
• Fritschy, J-M, D. K. Johnson, H. Mohler, and U. Rudolph. Independent assembly and subcellular targeting of GABAA-receptor subtypes demonstrated in mouse hippocampal and olfactory neurons. Neurosci. Letters:, 249: 99-102, 1998.
• Schultze, A.E., Poppenga, R.H., and Johnson, D.K. Alterations in serum and tissue iron profiles associated with mutations in the fitness14226SB locus of mice. Comp. Haemat. International 8: 72-76, 1998.
• Russell, L.B., Hunsicker, P.R., Johnson, D.K., and Shelby, M.D. Unlike other chemicals, etoposide (a topoisomerase-II inhibitor) produces peak mutagenicity in primary spermatocytes of the mouse. Mutat. Res. 400: 279-286, 1998.
• Rikke, B. A., D. K. Johnson, and T. E. Johnson. Molecular genetic architecture of the murine albino-deletion complex: High-resolution microsatellite map and genetically-anchored YAC framework map. Genetics., 147 (2), 787-799, 1997.
• Wu, M., E. M. Rinchik, E. Wilkinson, and D. K. Johnson. Inherited somatic mosaicism caused by an intracisternal A particle (IAP) insertion in the mouse tyrosinase gene. Proc. Natl. Acad. Sci., USA, 94: 890-894, 1997.
• Dhar, M. S., and D. K. Johnson. A microsatellite map of the pink-eyed dilution (p) complex in mouse chromosome 7. Mamm. Genome, 8: 143-145, 1997.
• Potter, M. D., S. G. Shinpock, R. A. Popp, D. M. Popp, V. Godfrey, D. A. Carpenter, A. Bernstein, D. K. Johnson, and E. M. Rinchik. Mutations in the murine fitness1 gene results in defective hematopoiesis. Blood, 90, 1850-1857, 1997.
• Johnson, D. K., L. J. Stubbs, C. T. Culiat, C. S. Montgomery, L. B. Russell, and E. M. Rinchik. Molecular analysis of 36 mutations at the mouse pink-eyed dilution (p) locus. Genetics, 141: 1563-1571, 1995.
• Russell, L. B., C. S. Montgomery, N.L.A. Cacheiro, and D. K. Johnson. Complementation analyses for 45 mutations encompassing the pink-eyed dilution (p) locus of the mouse. Genetics, 141: 1547-1562, 1995.

• Fritschy, J-M., D. Benke, D. K. Johnson, H. Mohler, and U. Rudolph. Essential role of the GABAA-receptor a-subunit for receptor formation demonstrated in mutant mice. J. Neuroscience, 4:1043-53, 1997.
• Allison, D. P., P. S. Kerper, M. J. Doktycz, T. Thundat, P. Modrich, F. W. Larimer, D. K. Johnson, P. R. Hoyt, M. L. Mucenski, and R. J. Warmack. Mapping individual cosmid DNAs by direct AFM imaging. Genomics 41: 379-384, 1997.
• Johnson, K. R., D. K. Johnson, E. M. Rinchik, M. Thayer, and E. J. Lewis. Mapping of the ARIX homeodomain gene to mouse chromosome 7 and human chromosome 11q13. Genomics, 33: 527-531, 1996.
• Johnson, D. K., L. J. Stubbs, and J. A. DeLoia. The mouse cyclin E maps to Chromosome 7 Mamm. Genome, 7:245, 1995.
• Stubbs, L., E. K. Rinchik, E. Goldberg, B. Rudy, M. A. Handel, and D. K. Johnson. Clustering of six human 11p15 gene homologs within a 500 kb interval of proximal mouse chromosome 7. Genomics, 24: 324-332, 1994.
• Rothstein, J., D. Johnson, J. Jessee, J. Skowronski, J. DeLoia, D. Solter, and B. Knowles. Construction of primary and subtracted cDNA libraries from early mouse embryos. Methods in Enzymol., 225: 587-610, 1994.
• Culiat, C. T., E. M. Rinchik, R. P. Woychik, L. J. Stubbs, L. B. Russell, C. S. Montgomery, and D. K. Johnson. The b3 subunit of the GABAA receptor appears to be necessary for normal palate development in the mouse. Presented at the Eighth Mouse Genome Workshop, London, England, Nov. 8, 1994.
• Culiat, C.T., L. Stubbs, R.D. Nicholls, C.S. Montgomery, L.B. Russell, D.K. Johnson and E. M. Rinchik. Concordance between isolated cleft palate in mice and alterations within a region including the gene encoding the ß3 subunit of the type A g-aminobutyric acid receptor. Proc. Natl. Acad. Sci USA 90: 5105-5109, 1993.
• Rothstein, J. L., D. Johnson, J. DeLoia, J. Skowronski, D. Solter, and B. Knowles. Gene expression during preimplantation mouse development. Genes and Devel., 6: 1190-1201, 1992.
• Rinchik, E.M., D.K. Johnson, F. L. Margolis, I.J. Jackson, L. B. Russell, and D. Carpenter. Reverse genetics in the mouse and its application to the study of deafness. In: Genetics of Hearing Impairment, ed. by. R. J. Ruben, T. R. Van De Water, and K. P. Steel, Annals of New York Academy of Sciences, vol 630, pp. 80-92, 1991.
• Scrable, H. J., D. K. Johnson, E. M. Rinchik, and W. K. Cavenee. Rhabdomyosarcoma-associated locus and MYOD1 are syntenic but separate loci on the short arm of human chromosome 11. Proc. Natl. Acad. Sci. USA, 87: 2182-2186, 1990.
• Rinchik, E.M., Machanoff, R., Cummings, C.C., and Johnson, D. K. Molecular cloning and mapping of the ecotropic leukemia provirus Emv-23 provides molecular access to the albino-deletion complex in mouse Chromosome 7. Genomics 4: 251-258, 1989.
• Johnson, D. K., R. E. Hand, Jr., E. M. Rinchik. Molecular mapping within the mouse albino-deletion complex. Proc. Natl. Acad. Sci. USA 86: 8862-8866, 1989.
• Rinchik, E. M., D. K. Johnson, M. L. Klebig, R. Machanoff, C. C. Cummings, A. K. Jimmerson, and D. A. Carpenter. Saturation-mutagenesis and physical-mapping strategies for regions of the mouse genome. In: Multilevel Health Effects Research - From Molecules to Man, ed. by J. F. Park and R. A. Pelroy. Battelle Press, Columbus, Ohio, pp. 91-96, 1989.