Genetic Ablation of a Mouse Gene Expressed Specifically in Brain

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 1990 Feb 1

PMID 2303033

Citations 26

Authors

D M Kingsley

E M Rinchik

L B Russell

H P Ottiger

J G Sutcliffe

N G Copeland

N A Jenkins

Affiliations

Soon will be listed here.

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.

Citing Articles

Feasibility of Ex Vivo Ligandomics.

Waduge P, Veettil R, Zhang B, Huang C, Tian H, Li W Biomolecules. 2025; 15(1).

PMID: 39858539 PMC: 11763836. DOI: 10.3390/biom15010145.

Secretogranin III: a promising therapeutic target for intraocular neovascular lesions.

Yuan C, Zuo L, Dong Y, Liu B, Qi H Int Ophthalmol. 2025; 45(1):26.

PMID: 39832055 PMC: 11746947. DOI: 10.1007/s10792-024-03393-2.

Secretogranin III Selectively Promotes Vascular Leakage in the Deep Vascular Plexus of Diabetic Retinopathy.

Ji L, Waduge P, Wu Y, Huang C, Kaur A, Oliveira P Int J Mol Sci. 2023; 24(13).

PMID: 37445707 PMC: 10341987. DOI: 10.3390/ijms241310531.

Safety and Efficacy of Systemic Anti-Scg3 Therapy to Treat Oxygen-Induced Retinopathy.

Dai C, Tian H, Bhatt A, Su G, Webster K, Li W Front Biosci (Landmark Ed). 2022; 27(4):130.

PMID: 35468689 PMC: 9201993. DOI: 10.31083/j.fbl2704130.

Neurovascular abnormalities in retinopathy of prematurity and emerging therapies.

Dai C, Xiao J, Wang C, Li W, Su G J Mol Med (Berl). 2022; 100(6):817-828.

PMID: 35394143 PMC: 9205172. DOI: 10.1007/s00109-022-02195-2.

References

Russell L . Functional and structural analyses of mouse genomic regions screened by the morphological specific-locus test. Mutat Res. 1989; 212(1):23-32. DOI: 10.1016/0027-5107(89)90019-5. View

Rinchik E, Russell L, Copeland N, Jenkins N . Molecular genetic analysis of the dilute-short ear (d-se) region of the mouse. Genetics. 1986; 112(2):321-42. PMC: 1202704. DOI: 10.1093/genetics/112.2.321. View

Ruppert S, Muller G, Kwon B, Schutz G . Multiple transcripts of the mouse tyrosinase gene are generated by alternative splicing. EMBO J. 1988; 7(9):2715-22. PMC: 457061. DOI: 10.1002/j.1460-2075.1988.tb03125.x. View

Henkemeyer M, Gertler F, Goodman W, Hoffmann F . The Drosophila Abelson proto-oncogene homolog: identification of mutant alleles that have pleiotropic effects late in development. Cell. 1987; 51(5):821-8. DOI: 10.1016/0092-8674(87)90105-x. View

Feinberg A, Vogelstein B . "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984; 137(1):266-7. DOI: 10.1016/0003-2697(84)90381-6. View

Kuehn M, Bradley A, Robertson E, Evans M . A potential animal model for Lesch-Nyhan syndrome through introduction of HPRT mutations into mice. Nature. 1987; 326(6110):295-8. DOI: 10.1038/326295a0. View

Siracusa L, Russell L, Jenkins N, Copeland N . Allelic variation within the Emv-15 locus defines genomic sequences closely linked to the agouti locus on mouse chromosome 2. Genetics. 1987; 117(1):85-92. PMC: 1203190. DOI: 10.1093/genetics/117.1.85. View

Shortle D, Haber J, Botstein D . Lethal disruption of the yeast actin gene by integrative DNA transformation. Science. 1982; 217(4557):371-3. DOI: 10.1126/science.7046050. View

RUSSELL W . X-ray-induced mutations in mice. Cold Spring Harb Symp Quant Biol. 1951; 16:327-36. DOI: 10.1101/sqb.1951.016.01.024. View

10.

Rothstein R . One-step gene disruption in yeast. Methods Enzymol. 1983; 101:202-11. DOI: 10.1016/0076-6879(83)01015-0. View

11.

Goebl M, Petes T . Most of the yeast genomic sequences are not essential for cell growth and division. Cell. 1986; 46(7):983-92. DOI: 10.1016/0092-8674(86)90697-5. View

12.

Avner P, Amar L, Dandolo L, Guenet J . Genetic analysis of the mouse using interspecific crosses. Trends Genet. 1988; 4(1):18-23. DOI: 10.1016/0168-9525(88)90123-0. View

13.

Capecchi M . The new mouse genetics: altering the genome by gene targeting. Trends Genet. 1989; 5(3):70-6. DOI: 10.1016/0168-9525(89)90029-2. View

14.

ONeill A, Reid K, GARBERI J, Karl M, Flaherty L . Extensive deletions in the Q region of the mouse major histocompatibility complex. Immunogenetics. 1986; 24(6):368-73. DOI: 10.1007/BF00377954. View

15.

Russell L . 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; 11(1):107-23. DOI: 10.1016/0027-5107(71)90036-4. View

16.

Kingsley D, Jenkins N, Copeland N . A molecular genetic linkage map of mouse chromosome 9 with regional localizations for the Gsta, T3g, Ets-1 and Ldlr loci. Genetics. 1989; 123(1):165-72. PMC: 1203779. DOI: 10.1093/genetics/123.1.165. View

17.

Prochazka M, Kozak U, Kozak L . A glycerol-3-phosphate dehydrogenase null mutant in BALB/cHeA mice. J Biol Chem. 1989; 264(8):4679-83. View

18.

Buchberg A, Bedigian H, Taylor B, Brownell E, Ihle J, Nagata S . 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):149-65. View

19.

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; 326(6110):292-5. DOI: 10.1038/326292a0. View

20.

Jenkins N, Copeland N, Taylor B, Lee B . Organization, distribution, and stability of endogenous ecotropic murine leukemia virus DNA sequences in chromosomes of Mus musculus. J Virol. 1982; 43(1):26-36. PMC: 256092. DOI: 10.1128/JVI.43.1.26-36.1982. View