A Mouse Knockout Library for Secreted and Transmembrane Proteins

Overview

Journal Nat Biotechnol

Specialty Biotechnology

Date 2010 Jun 22

PMID 20562862

Citations 198

Authors

Tracy Tang

Li Li

Jerry Tang

Yun Li

Wei Yu Lin

Flavius Martin

Deanna Grant

Mark Solloway

Leon Parker

Weilan Ye

William Forrest

Nico Ghilardi

Tamas Oravecz

Kenneth A Platt

Dennis S Rice

Gwenn M Hansen

Alejandro Abuin

Derek E Eberhart

Paul Godowski

Kathleen H Holt

Andrew Peterson

Brian P Zambrowicz

Frederic J de Sauvage

Affiliations

Soon will be listed here.

Abstract

Large collections of knockout organisms facilitate the elucidation of gene functions. Here we used retroviral insertion or homologous recombination to disrupt 472 genes encoding secreted and membrane proteins in mice, providing a resource for studying a large fraction of this important class of drug target. The knockout mice were subjected to a systematic phenotypic screen designed to uncover alterations in embryonic development, metabolism, the immune system, the nervous system and the cardiovascular system. The majority of knockout lines exhibited altered phenotypes in at least one of these therapeutic areas. To our knowledge, a comprehensive phenotypic assessment of a large number of mouse mutants generated by a gene-specific approach has not been described previously.

Citing Articles

Characteristics of blood-brain barrier heterogeneity between brain regions revealed by profiling vascular and perivascular cells.

Pfau S, Langen U, Fisher T, Prakash I, Nagpurwala F, Lozoya R Nat Neurosci. 2024; 27(10):1892-1903.

PMID: 39210068 PMC: 11452347. DOI: 10.1038/s41593-024-01743-y.

Co-transfection of murine NXPE2 and murine glycophorin A confers reactivity with Ter-119.

Keele G, Hay A, Holness N, Jash A, Ewald S, OConnor C Haematologica. 2024; 109(11):3755-3759.

PMID: 39021224 PMC: 11532708. DOI: 10.3324/haematol.2024.285168.

Thyrotropin-Releasing Hormone and Food Intake in Mammals: An Update.

Vargas Y, Castro Tron A, Rodriguez Rodriguez A, Uribe R, Joseph-Bravo P, Charli J Metabolites. 2024; 14(6).

PMID: 38921437 PMC: 11205479. DOI: 10.3390/metabo14060302.

Combined genetic-pharmacologic inactivation of tightly linked ADAMTS proteases in temporally specific windows uncovers distinct roles for versican proteolysis and glypican-6 in cardiac development.

Mead T, Bhutada S, Foulcer S, Peruzzi N, Nelson C, Seifert D Matrix Biol. 2024; 131:1-16.

PMID: 38750698 PMC: 11526477. DOI: 10.1016/j.matbio.2024.05.003.

Context-Specific Stress Causes Compartmentalized SARM1 Activation and Local Degeneration in Cortical Neurons.

Hinz F, Villegas C, Roberts J, Yao H, Gaddam S, Delwig A J Neurosci. 2024; 44(24).

PMID: 38692735 PMC: 11170950. DOI: 10.1523/JNEUROSCI.2424-23.2024.

References

Scott H, Kudoh J, Wattenhofer M, Shibuya K, Berry A, Chrast R . Insertion of beta-satellite repeats identifies a transmembrane protease causing both congenital and childhood onset autosomal recessive deafness. Nat Genet. 2001; 27(1):59-63. DOI: 10.1038/83768. View

Friedman L, Dror A, Avraham K . Mouse models to study inner ear development and hereditary hearing loss. Int J Dev Biol. 2007; 51(6-7):609-31. DOI: 10.1387/ijdb.072365lf. View

Morgan H, Beck T, Blake A, Gates H, Adams N, Debouzy G . EuroPhenome: a repository for high-throughput mouse phenotyping data. Nucleic Acids Res. 2009; 38(Database issue):D577-85. PMC: 2808931. DOI: 10.1093/nar/gkp1007. View

Cordes S . N-ethyl-N-nitrosourea mutagenesis: boarding the mouse mutant express. Microbiol Mol Biol Rev. 2005; 69(3):426-39. PMC: 1197804. DOI: 10.1128/MMBR.69.3.426-439.2005. View

Su A, Wiltshire T, Batalov S, Lapp H, Ching K, Block D . A gene atlas of the mouse and human protein-encoding transcriptomes. Proc Natl Acad Sci U S A. 2004; 101(16):6062-7. PMC: 395923. DOI: 10.1073/pnas.0400782101. View

Wattler S, Kelly M, Nehls M . Construction of gene targeting vectors from lambda KOS genomic libraries. Biotechniques. 1999; 26(6):1150-6, 1158, 1160. DOI: 10.2144/99266rr02. View

Austin C, Battey J, Bradley A, Bucan M, Capecchi M, Collins F . The knockout mouse project. Nat Genet. 2004; 36(9):921-4. PMC: 2716027. DOI: 10.1038/ng0904-921. View

Beigneux A, Davies B, Gin P, Weinstein M, Farber E, Qiao X . Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 plays a critical role in the lipolytic processing of chylomicrons. Cell Metab. 2007; 5(4):279-91. PMC: 1913910. DOI: 10.1016/j.cmet.2007.02.002. View

Friedel R, Seisenberger C, Kaloff C, Wurst W . EUCOMM--the European conditional mouse mutagenesis program. Brief Funct Genomic Proteomic. 2007; 6(3):180-5. DOI: 10.1093/bfgp/elm022. View

10.

Friddle C, Abuin A, Ramirez-Solis R, Richter L, Buxton E, Edwards J . High-throughput mouse knockouts provide a functional analysis of the genome. Cold Spring Harb Symp Quant Biol. 2004; 68:311-5. DOI: 10.1101/sqb.2003.68.311. View

11.

Cheng A, Rowley B, Pao W, Hayday A, Bolen J, Pawson T . Syk tyrosine kinase required for mouse viability and B-cell development. Nature. 1995; 378(6554):303-6. DOI: 10.1038/378303a0. View

12.

Colonna M, Samaridis J, Angman L . Molecular characterization of two novel C-type lectin-like receptors, one of which is selectively expressed in human dendritic cells. Eur J Immunol. 2000; 30(2):697-704. DOI: 10.1002/1521-4141(200002)30:2<697::AID-IMMU697>3.0.CO;2-M. View

13.

Fan B, Brennan J, Grant D, Peale F, Rangell L, Kirchhofer D . Hepatocyte growth factor activator inhibitor-1 (HAI-1) is essential for the integrity of basement membranes in the developing placental labyrinth. Dev Biol. 2006; 303(1):222-30. DOI: 10.1016/j.ydbio.2006.11.005. View

14.

Yan M, Plowman G . Delta-like 4/Notch signaling and its therapeutic implications. Clin Cancer Res. 2007; 13(24):7243-6. DOI: 10.1158/1078-0432.CCR-07-1393. View

15.

Waterston R, Lindblad-Toh K, Birney E, Rogers J, Abril J, Agarwal P . Initial sequencing and comparative analysis of the mouse genome. Nature. 2002; 420(6915):520-62. DOI: 10.1038/nature01262. View

16.

Brown S, Chambon P, Hrabe de Angelis M . EMPReSS: standardized phenotype screens for functional annotation of the mouse genome. Nat Genet. 2005; 37(11):1155. DOI: 10.1038/ng1105-1155. View

17.

Brommage R . Validation and calibration of DEXA body composition in mice. Am J Physiol Endocrinol Metab. 2003; 285(3):E454-9. DOI: 10.1152/ajpendo.00470.2002. View

18.

May F, Hagedorn I, Pleines I, Bender M, Vogtle T, Eble J . CLEC-2 is an essential platelet-activating receptor in hemostasis and thrombosis. Blood. 2009; 114(16):3464-72. DOI: 10.1182/blood-2009-05-222273. View

19.

Wilson L, Ching Y, Farias M, Hartford S, Howell G, Shao H . Random mutagenesis of proximal mouse chromosome 5 uncovers predominantly embryonic lethal mutations. Genome Res. 2005; 15(8):1095-105. PMC: 1182222. DOI: 10.1101/gr.3826505. View

20.

Zambrowicz B, Friedrich G, Buxton E, Lilleberg S, Person C, Sands A . Disruption and sequence identification of 2,000 genes in mouse embryonic stem cells. Nature. 1998; 392(6676):608-11. DOI: 10.1038/33423. View