Hostname: page-component-7479d7b7d-t6hkb Total loading time: 0 Render date: 2024-07-12T03:57:51.377Z Has data issue: false hasContentIssue false
  • English
  • Français

Mini-mouse: phenotypic characterization of a transgenic insertional mutant allelic to pygmy

Published online by Cambridge University Press:  14 April 2009

Kathleen F. Benson  and
Kiran Chada
Kathleen F. Benson
Affiliation:
Department of Biochemistry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, 675 Hoes Lane, Piscataway, NJ 08854-5635, USA
Kiran Chada
Affiliation:
Department of Biochemistry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, 675 Hoes Lane, Piscataway, NJ 08854-5635, USA

Summary

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

A phenotypic analysis was performed on two alleles at the pygmy locus which arose by insertional mutagenesis in transgenic mice. Similar to the spontaneous mutant pygmy, the adult insertional transgenic mutants are 40% of the size of wild-type litter-mates whereas adult heterozygotes are 80% of wild-type litter-mates. An analysis of the various organs revealed that, in general, there was a reduction in weight of each organ commensurate with the overall reduction in body size. However, two organs did not follow this pattern, the brain being disproportionately larger and the adrenals disproportionately smaller in the mutant mice. In addition, mini-mice have less adipose tissue than their wild-type or heterozygous litter-mates. A developmental analysis determined that mutants could first be identified on the basis of reduced body weight at day 15·5 of gestation. The small size is not due to a growth hormone deficiency so these mice differ from other known dwarf mouse mutants. Therefore they should provide insight into the growth hormone-resistant human dwarnsms and help in furthering our knowledge of mammalian growth and development.

Type
Research Article
Information
Genetics Research , Volume 64 , Issue 1 , August 1994 , pp. 27 - 33
Copyright
Copyright © Cambridge University Press 1994

References

Baker, J., Jeh-Ping, L., Robertson, E. J., & Efstratiadis, A., (1993). Role of insulin-like growth factors in embryonic and postnatal growth. Cell 75, 73–82.CrossRefGoogle ScholarPubMed
Behringer, R. R., Lewin, T. M., Quaife, C. J., Palmiter, R. D., Brinster, R. L., &D'Ercole, A. J., (1990). Expression of insulin-like growth factor I stimulates normal somatic growth in growth hormone-deficient transgenic mice. Endocrinology 127, 1033–1040.CrossRefGoogle ScholarPubMed
Chubb, C., & Nolan, C., (1985). Animal models of male infertility: mice bearing single-gene mutations that induce infertility. Endocrinology 117, 338–346.CrossRefGoogle ScholarPubMed
Eicher, E. M., & Beamer, W. G., (1976). Inherited ateliotic dwarfism in mice. Journal of Heredity 67, 87–91.CrossRefGoogle ScholarPubMed
Encyclopedia of the Mouse Genome III (1993). Mammalian Genome 4, special issue.Google Scholar
Escobar, V., Gleiser, S., & Weaver, D. D., (1978). Phenotypic and genetic analysis of the Silver-Russell syndrome. Clinical Genetics 13, 278–288.CrossRefGoogle ScholarPubMed
Francke, U., Hsieh, C., Kelly, D., Lai, E., & Popko, B., (1992). Induced reciprocal translocation in transgenic mice near sites of transgene integration. Mammalian Genome 3, 209–216.CrossRefGoogle ScholarPubMed
Girard, J., (1989). Hormonal regulation of fetal growth. In Intrauterine Growth Retardation (ed. Senterre, J.), pp. 23–37. New York: Raven Press.Google Scholar
Glasscock, G. F., Gelber, S. E., Lamson, G., McGee-Tekula, R., & Rosenfeld, R. G., (1990). Pituitary control of growth in the neonatal rat: effects of neonatal hypophysectomy on somatic and organ growth, serum insulin-like growth factors (IGF)-I and -II levels, and expression of IGF binding proteins. Endocrinology 127, 1792–1803.CrossRefGoogle ScholarPubMed
Glasscock, G. F., Gin, K. K. L., Kim, J. D., Hintz, R. L., & Rosenfeld, R. G., (1991). Ontogeny of pituitary regulation of growth in the developing rat: comparison of effects of hypophysectomy and hormone replacement on somatic and organ growth, serum insulin-like growth factor-I (IGF-I) and IGF-II levels, and IGF-binding protein levels in the neonatal and juvenile rat. Endocrinology 128, 1036–1047.CrossRefGoogle ScholarPubMed
Gordon, J. W., Pravtcheva, D., Poorman, P. A., Moses, M. J., Brock, W. A., & Ruddle, F. H., (1989). Association of foreign DNA sequence with male sterility and translocation in a line of transgenic mice. Somatic Cell and Molecular Genetics 15(6), 569–578.CrossRefGoogle Scholar
Green, M. C., (1989). Catalog of mutant genes and polymorphic loci. In Genetic Variants and Strains of the Laboratory Mouse, Second Ed. (ed. Lyon, M. F., and Searle, A. G.), pp. 87–88, 94–95. 205–206, 281. New York: Oxford University Press.Google Scholar
Hogan, B., Costantini, F., & Lacy, E., (1986). Manipulating the Mouse Embryo, A Laboratory Manual. New York: Cold Spring Harbor Laboratory.Google Scholar
Jeh-Ping, L., Baker, J., Perkins, A. S., Robertson, E. J., & Efstratiadis, A., (1993). Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r). Cell 75, 59–72.Google Scholar
Justice, M. J., Siracusa, L. D., Gilbert, D. J., Heisterkamp, N., Groffen, J., Chada, K., Silan, C. M., Copeland, N. G., & Jenkins, N. A., (1990). A genetic linkage map of mouse chromosome 10: location of eighteen molecular markers using a single interspecific backcross. Genetics 125, 855–866.CrossRefGoogle ScholarPubMed
Kannan, C. R., (1988). Clinical Surveys in Endocrinology Volume 2, The Adrenal Gland, pp. 424–459. New York: Plenum Publishing Corporation.Google Scholar
Kenyon, C., (1988). The nematode Caenorhabditis elegans. Science 240, 1448–1453.CrossRefGoogle ScholarPubMed
King, J. W. B., (1955). Observations on the mutant ‘pygmy’ in the house mouse. Genetics 53, 487–497.Google Scholar
Lalley, P. A., Davisson, M. T., Graves, J. A. M., O'Brien, S. J., Roderick, T. H., Doolittle, D. P., & Hillyard, A. L., (1988). Report of the committee on comparative mapping. Cytogenetics and Cell Genetics 49, 227–235.CrossRefGoogle Scholar
MacArthur, J. W., (1944). Genetics of body size and related characters. American Naturalist 78, 142–157.CrossRefGoogle Scholar
Mahon, K. A., Overbeek, P. A., & Westphal, H., (1988). Prenatal lethality in a transgenic mouse line is the result of a chromosomal translocation. Proceedings of the National Academy of Sciences, USA 85, 1165–1168.CrossRefGoogle Scholar
Marks, L. J., & Bergeson, P. S., (1977). The Silver-Russell syndrome. American Journal of Diseases of Children 131, 447–451.CrossRefGoogle Scholar
McKusick, V. A., (1990). Mendelian Inheritance in Man, 9th Edition. Baltimore: Johns Hopkins University Press.Google Scholar
McNeish, J. D., Thayer, J., Walling, K., Sulik, K. K., Potter, S. S., & Scott, W. J., (1990). Phenotypic characterization of the transgenic mouse insertional mutation, legless. Journal of Experimental Zoology 253, 151–162.CrossRefGoogle ScholarPubMed
Meisler, M. H., (1992). Insertional mutagenesis of ‘classical’ and novel genes in transgenic mice. Trends in Genetics 8(10), 341–344.Google ScholarPubMed
Palmiter, R. D., & Brinster, R. L., (1986). Germ-line transformation of mice. Annual Review of Genetics 20, 465–499.CrossRefGoogle ScholarPubMed
Palmiter, R. D., Brinster, R. L., Hammer, R. E., Trumbauer, M. E., Rosenfeld, M. G., Birnberg, N. C., & Evans, R. M., (1982). Dramatic growth of mice that develop from eggs microinjected with metallothionein–growth hormone fusion genes. Nature 300, 611–615.CrossRefGoogle ScholarPubMed
Powell-Braxton, L., Hollingshead, P., Warburton, C., Dowd, M., Pitts-Meek, S., Dalton, D., Gillett, N., & Stewart, T. A., (1993). IGF-1 is required for normal embryonic growth in mice. Genes and Development 7, 2609–2617.CrossRefGoogle ScholarPubMed
Quaife, C. J., Mathews, L. S., Pinkert, C. A., Hammer, R. E., Brinster, R. L., & Palmiter, R. D., (1989). Histopathology associated with elevated levels of growth hormone and insulin-like growth factor I in transgenic mice. Endocrinology 124, 40–48.CrossRefGoogle ScholarPubMed
Ratty, A. K., Fitzgerald, L. W., Titeler, M., Glick, S. D., Mullins, J. J., & Gross, K. W., (1990). Circling behavior exhibited by a transgenic insertional mutant. Molecular Brain Research 8, 355–358.CrossRefGoogle ScholarPubMed
Reith, A. D., & Bernstein, A., (1991). Molecular basis of mouse developmental mutants. Genes and Development 5, 1115–1123.CrossRefGoogle ScholarPubMed
Rogers, P., & Webb, G. P., (1980). Estimation of body fat in normal and obese mice. British Journal of Nutrition 43, 83–86.CrossRefGoogle ScholarPubMed
Rubin, G. M., (1988). Drosophila melanogaster as an experimental organism. Science 240, 1453–1459.CrossRefGoogle ScholarPubMed
Russell, A., (1954). A syndrome of ‘intra-uterine’ dwarfism recognizable at birth with cranio-facial dysostosis, disproportionately short arms, and other anomalies (5 examples). Proceedings of the Royal Society of Medicine 47, 1040–1043.Google ScholarPubMed
Sambrook, J., Fritsch, E. F., & Maniatis, T., (1989). Molecular Cloning, A Laboratory Manual, Second Edition. New York: Cold Spring Harbor Laboratory Press.Google Scholar
Shea, B. T., Hammer, R. E., & Brinster, R. L., (1987). Growth allometry of the organs in giant transgenic mice. Endocrinology 121, 1924–1930.CrossRefGoogle ScholarPubMed
Silver, H. K., Kiyasu, W., George, J., & Deamer, W. C., (1953). Syndrome of congenital hemihypertrophy, shortness of stature, and elevated urinary gonadotrophins. Pediatrics 12, 368–375.CrossRefGoogle Scholar
Sinha, Y. N., Wolff, G. L., Baxter, S. R., & Domon, O. E., (1979). Serum and pituitary concentrations of growth hormone and prolactin in pygmy mice. Proceedings of the Society for Experimental Biology and Medicine 162, 221–223.CrossRefGoogle ScholarPubMed
Tanner, J. M., Lejarraga, H., & Cameron, N., (1975). The natural history of the Silver—Russell syndrome: a longitudinal study of thirty-nine cases. Pediatric Research 9, 611–623.CrossRefGoogle ScholarPubMed
Taylor, B. A., & Grieco, D., (1991). Localization of the gene encoding insulin-like growth factor I on mouse chromosome 10. Cytogenetics and Cell Genetics 56, 57–58.CrossRefGoogle ScholarPubMed
Thomas, P. S., & Farquhar, M. N., (1978). Specific measurement of DNA in nuclei and nucleic acids using diaminobenzoic acid. Analytical Biochemistry 89, 35–44.CrossRefGoogle ScholarPubMed
Warwick, E. J., & Lewis, W. L., (1954). Increase in frequency of a deleterious recessive gene in mice. Journal of Heredity 45, 143–145.CrossRefGoogle Scholar
Xiang, X., Benson, K. F., & Chada, K., (1990). Mini-mouse: disruption of the pygmy locus i n a transgenic insertional mutant. Science 247, 967–969.CrossRefGoogle Scholar