Influence of genetic background on genetically engineered mouse phenotypes

Research output: Chapter in Book/Report/Conference proceedingChapter

111 Citations (Scopus)

Abstract

The history of mouse genetics, which involves the study of strain-dependent phenotype variability, makes it clear that the genetic background onto which a gene-targeted allele is placed can cause considerable variation in genetically engineered mouse (GEM) phenotype. This variation can present itself as completely different phenotypes, as variations in penetrance of phenotype, or as variable expressivity of phenotype. In this chapter we provide examples from gene-targeting literature showing each of these types of phenotype variation. We discuss ways in which modifier genes can affect the phenotype of a mouse with a mutant gene, and we give examples of modifier locus identification. We also review approaches to minimize gene polymorphism and flanking gene differences between experimental animals, and between them and their controls. In addition, we discuss the advantages and disadvantages of performing the first analysis of a knockout mouse on a mixed genetic background. We conclude that a mixed background provides the quickest preview of possible strain-dependent phenotypes (1, 2). Finally, we review recent approaches to improving genetic diversity by generating new inbred strains that encompass a broader range of alleles within the mouse species.

Original languageEnglish (US)
Title of host publicationMethods in Molecular Biology
Pages423-433
Number of pages11
Volume530
DOIs
StatePublished - 2009

Publication series

NameMethods in Molecular Biology
Volume530
ISSN (Print)10643745

Fingerprint

Phenotype
Genes
Alleles
Modifier Genes
Gene Targeting
Genetic Background
Penetrance
Knockout Mice
History

Keywords

  • expressivity
  • genetic background
  • genetic engineering
  • Knockout
  • modifier gene
  • mouse
  • penetrance

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

Cite this

Doetschman, T. C. (2009). Influence of genetic background on genetically engineered mouse phenotypes. In Methods in Molecular Biology (Vol. 530, pp. 423-433). (Methods in Molecular Biology; Vol. 530). https://doi.org/10.1007/978-1-59745-471-1_23

Influence of genetic background on genetically engineered mouse phenotypes. / Doetschman, Thomas C.

Methods in Molecular Biology. Vol. 530 2009. p. 423-433 (Methods in Molecular Biology; Vol. 530).

Research output: Chapter in Book/Report/Conference proceedingChapter

Doetschman, TC 2009, Influence of genetic background on genetically engineered mouse phenotypes. in Methods in Molecular Biology. vol. 530, Methods in Molecular Biology, vol. 530, pp. 423-433. https://doi.org/10.1007/978-1-59745-471-1_23
Doetschman TC. Influence of genetic background on genetically engineered mouse phenotypes. In Methods in Molecular Biology. Vol. 530. 2009. p. 423-433. (Methods in Molecular Biology). https://doi.org/10.1007/978-1-59745-471-1_23
Doetschman, Thomas C. / Influence of genetic background on genetically engineered mouse phenotypes. Methods in Molecular Biology. Vol. 530 2009. pp. 423-433 (Methods in Molecular Biology).
@inbook{bcd3c533e4744525bc2ad269beb0beca,
title = "Influence of genetic background on genetically engineered mouse phenotypes",
abstract = "The history of mouse genetics, which involves the study of strain-dependent phenotype variability, makes it clear that the genetic background onto which a gene-targeted allele is placed can cause considerable variation in genetically engineered mouse (GEM) phenotype. This variation can present itself as completely different phenotypes, as variations in penetrance of phenotype, or as variable expressivity of phenotype. In this chapter we provide examples from gene-targeting literature showing each of these types of phenotype variation. We discuss ways in which modifier genes can affect the phenotype of a mouse with a mutant gene, and we give examples of modifier locus identification. We also review approaches to minimize gene polymorphism and flanking gene differences between experimental animals, and between them and their controls. In addition, we discuss the advantages and disadvantages of performing the first analysis of a knockout mouse on a mixed genetic background. We conclude that a mixed background provides the quickest preview of possible strain-dependent phenotypes (1, 2). Finally, we review recent approaches to improving genetic diversity by generating new inbred strains that encompass a broader range of alleles within the mouse species.",
keywords = "expressivity, genetic background, genetic engineering, Knockout, modifier gene, mouse, penetrance",
author = "Doetschman, {Thomas C}",
year = "2009",
doi = "10.1007/978-1-59745-471-1_23",
language = "English (US)",
isbn = "9781934115268",
volume = "530",
series = "Methods in Molecular Biology",
pages = "423--433",
booktitle = "Methods in Molecular Biology",

}

TY - CHAP

T1 - Influence of genetic background on genetically engineered mouse phenotypes

AU - Doetschman, Thomas C

PY - 2009

Y1 - 2009

N2 - The history of mouse genetics, which involves the study of strain-dependent phenotype variability, makes it clear that the genetic background onto which a gene-targeted allele is placed can cause considerable variation in genetically engineered mouse (GEM) phenotype. This variation can present itself as completely different phenotypes, as variations in penetrance of phenotype, or as variable expressivity of phenotype. In this chapter we provide examples from gene-targeting literature showing each of these types of phenotype variation. We discuss ways in which modifier genes can affect the phenotype of a mouse with a mutant gene, and we give examples of modifier locus identification. We also review approaches to minimize gene polymorphism and flanking gene differences between experimental animals, and between them and their controls. In addition, we discuss the advantages and disadvantages of performing the first analysis of a knockout mouse on a mixed genetic background. We conclude that a mixed background provides the quickest preview of possible strain-dependent phenotypes (1, 2). Finally, we review recent approaches to improving genetic diversity by generating new inbred strains that encompass a broader range of alleles within the mouse species.

AB - The history of mouse genetics, which involves the study of strain-dependent phenotype variability, makes it clear that the genetic background onto which a gene-targeted allele is placed can cause considerable variation in genetically engineered mouse (GEM) phenotype. This variation can present itself as completely different phenotypes, as variations in penetrance of phenotype, or as variable expressivity of phenotype. In this chapter we provide examples from gene-targeting literature showing each of these types of phenotype variation. We discuss ways in which modifier genes can affect the phenotype of a mouse with a mutant gene, and we give examples of modifier locus identification. We also review approaches to minimize gene polymorphism and flanking gene differences between experimental animals, and between them and their controls. In addition, we discuss the advantages and disadvantages of performing the first analysis of a knockout mouse on a mixed genetic background. We conclude that a mixed background provides the quickest preview of possible strain-dependent phenotypes (1, 2). Finally, we review recent approaches to improving genetic diversity by generating new inbred strains that encompass a broader range of alleles within the mouse species.

KW - expressivity

KW - genetic background

KW - genetic engineering

KW - Knockout

KW - modifier gene

KW - mouse

KW - penetrance

UR - http://www.scopus.com/inward/record.url?scp=65549093701&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=65549093701&partnerID=8YFLogxK

U2 - 10.1007/978-1-59745-471-1_23

DO - 10.1007/978-1-59745-471-1_23

M3 - Chapter

C2 - 19266333

AN - SCOPUS:65549093701

SN - 9781934115268

VL - 530

T3 - Methods in Molecular Biology

SP - 423

EP - 433

BT - Methods in Molecular Biology

ER -