Skip to main content
PMC home page
The EMBO Journal logoLink to The EMBO Journal
. 1990 Feb;9(2):395–399. doi: 10.1002/j.1460-2075.1990.tb08123.x

Genetic ablation of a mouse gene expressed specifically in brain.

D M Kingsley 1, E M Rinchik 1, L B Russell 1, H P Ottiger 1, J G Sutcliffe 1, N G Copeland 1, N A Jenkins 1
PMCID: PMC551679  PMID: 2303033

Abstract

The 1B1075 gene was initially identified from a cDNA clone of a rat brain messenger RNA expressed in particular subsets of CNS neurons and pituitary cells. Although the protein encoded by this gene is of unknown function, its sequence suggests that it may be related to secretogranin proteins, which are found in association with secretory granules in a variety of peptidergic endocrine and neuronal cells. Here we show that the mouse 1B1075 gene is located between the dilute (d) and short ear (se) genes on chromosome 9. Many different deletion mutations have previously been isolated in the genetic region that includes these genes. By producing mice carrying two deletions that overlap at the 1B1075 locus, the gene for this brain-specific message can be completely eliminated from otherwise viable animals. The animals missing the 1B1075 gene provide an important new tool for determining the function of this gene in the brain. In addition, these results provide a new molecular entry point for detailed characterization of other genes in the d-se region.

Full text

PDF
395

Images in this article

397Fig. 3.
on p.397
398Fig. 4.
on p.398
398Fig. 5.
on p.398

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Avner P., Amar L., Dandolo L., Guénet J. L. Genetic analysis of the mouse using interspecific crosses. Trends Genet. 1988 Jan;4(1):18–23. doi: 10.1016/0168-9525(88)90123-0. [DOI] [PubMed] [Google Scholar]
  2. Buchberg A. M., Bedigian H. G., Taylor B. A., Brownell E., Ihle J. N., Nagata S., Jenkins N. A., Copeland N. G. Localization of Evi-2 to chromosome 11: linkage to other proto-oncogene and growth factor loci using interspecific backcross mice. Oncogene Res. 1988;2(2):149–165. [PubMed] [Google Scholar]
  3. Buchberg A. M., Brownell E., Nagata S., Jenkins N. A., Copeland N. G. A comprehensive genetic map of murine chromosome 11 reveals extensive linkage conservation between mouse and human. Genetics. 1989 May;122(1):153–161. doi: 10.1093/genetics/122.1.153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Capecchi M. R. The new mouse genetics: altering the genome by gene targeting. Trends Genet. 1989 Mar;5(3):70–76. doi: 10.1016/0168-9525(89)90029-2. [DOI] [PubMed] [Google Scholar]
  5. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  6. Goebl M. G., Petes T. D. Most of the yeast genomic sequences are not essential for cell growth and division. Cell. 1986 Sep 26;46(7):983–992. doi: 10.1016/0092-8674(86)90697-5. [DOI] [PubMed] [Google Scholar]
  7. Henkemeyer M. J., Gertler F. B., Goodman W., Hoffmann F. M. The Drosophila Abelson proto-oncogene homolog: identification of mutant alleles that have pleiotropic effects late in development. Cell. 1987 Dec 4;51(5):821–828. doi: 10.1016/0092-8674(87)90105-x. [DOI] [PubMed] [Google Scholar]
  8. Hooper M., Hardy K., Handyside A., Hunter S., Monk M. HPRT-deficient (Lesch-Nyhan) mouse embryos derived from germline colonization by cultured cells. Nature. 1987 Mar 19;326(6110):292–295. doi: 10.1038/326292a0. [DOI] [PubMed] [Google Scholar]
  9. Jenkins N. A., Copeland N. G., Taylor B. A., Lee B. K. Organization, distribution, and stability of endogenous ecotropic murine leukemia virus DNA sequences in chromosomes of Mus musculus. J Virol. 1982 Jul;43(1):26–36. doi: 10.1128/jvi.43.1.26-36.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kingsley D. M., Jenkins N. A., Copeland N. G. A molecular genetic linkage map of mouse chromosome 9 with regional localizations for the Gsta, T3g, Ets-1 and Ldlr loci. Genetics. 1989 Sep;123(1):165–172. doi: 10.1093/genetics/123.1.165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kuehn M. R., Bradley A., Robertson E. J., Evans M. J. A potential animal model for Lesch-Nyhan syndrome through introduction of HPRT mutations into mice. Nature. 1987 Mar 19;326(6110):295–298. doi: 10.1038/326295a0. [DOI] [PubMed] [Google Scholar]
  12. O'Neill A. E., Reid K., Garberi J. C., Karl M., Flaherty L. Extensive deletions in the Q region of the mouse major histocompatibility complex. Immunogenetics. 1986;24(6):368–373. doi: 10.1007/BF00377954. [DOI] [PubMed] [Google Scholar]
  13. Prochazka M., Kozak U. C., Kozak L. P. A glycerol-3-phosphate dehydrogenase null mutant in BALB/cHeA mice. J Biol Chem. 1989 Mar 15;264(8):4679–4683. [PubMed] [Google Scholar]
  14. RUSSELL W. L. X-ray-induced mutations in mice. Cold Spring Harb Symp Quant Biol. 1951;16:327–336. doi: 10.1101/sqb.1951.016.01.024. [DOI] [PubMed] [Google Scholar]
  15. Rinchik E. M., Russell L. B., Copeland N. G., Jenkins N. A. Molecular genetic analysis of the dilute-short ear (d-se) region of the mouse. Genetics. 1986 Feb;112(2):321–342. doi: 10.1093/genetics/112.2.321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Rothstein R. J. One-step gene disruption in yeast. Methods Enzymol. 1983;101:202–211. doi: 10.1016/0076-6879(83)01015-0. [DOI] [PubMed] [Google Scholar]
  17. Ruppert S., Müller G., Kwon B., Schütz G. Multiple transcripts of the mouse tyrosinase gene are generated by alternative splicing. EMBO J. 1988 Sep;7(9):2715–2722. doi: 10.1002/j.1460-2075.1988.tb03125.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Russell L. B. Definition of functional units in a small chromosomal segment of the mouse and its use in interpreting the nature of radiation-induced mutations. Mutat Res. 1971 Jan;11(1):107–123. doi: 10.1016/0027-5107(71)90036-4. [DOI] [PubMed] [Google Scholar]
  19. Russell L. B. Functional and structural analyses of mouse genomic regions screened by the morphological specific-locus test. Mutat Res. 1989 May;212(1):23–32. doi: 10.1016/0027-5107(89)90019-5. [DOI] [PubMed] [Google Scholar]
  20. Shortle D., Haber J. E., Botstein D. Lethal disruption of the yeast actin gene by integrative DNA transformation. Science. 1982 Jul 23;217(4557):371–373. doi: 10.1126/science.7046050. [DOI] [PubMed] [Google Scholar]
  21. Siracusa L. D., Russell L. B., Jenkins N. A., Copeland N. G. Allelic variation within the Emv-15 locus defines genomic sequences closely linked to the agouti locus on mouse chromosome 2. Genetics. 1987 Sep;117(1):85–92. doi: 10.1093/genetics/117.1.85. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES