• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Gene targeting yields a CD18-mutant mouse for study of inflammation.

CD18 is the common beta subunit for the heterodimeric leukocyte integrins that mediate many inflammatory cell adhesion responses including binding to intercellular adhesion molecules 1 and 2. CD18 deficiency in humans causes a severe granulocyte disorder with susceptibility to bacterial infections and high morbidity and mortality. Gene targeting was used to prepare an insertion mutation in the murine CD18 gene. The insertion mutation resulted in a hypomorphic rather than a null allele due to low expression from a cryptic promoter in the plasmid construct. Homozygous mutant mice are viable and fertile, demonstrate a mild granulocytosis, and have 2 or 16% of normal CD18 expression on granulocytes in the resting or activated state, respectively. Mutant mice show an impaired inflammatory response to a chemical peritonitis and delayed rejection of cardiac transplants. These CD18-mutant mice provide a model of the moderate form of the human disease and should be extremely valuable for in vivo analysis of the role of leukocyte integrin-dependent adhesion in inflammatory disease models.

Pubmed ID: 8101543

Authors

  • Wilson RW
  • Ballantyne CM
  • Smith CW
  • Montgomery C
  • Bradley A
  • O'Brien WE
  • Beaudet AL

Journal

Journal of immunology (Baltimore, Md. : 1950)

Publication Data

August 1, 1993

Associated Grants

  • Agency: NHLBI NIH HHS, Id: K08-HL-02537
  • Agency: NIAMS NIH HHS, Id: K11-AR-01813
  • Agency: NIAID NIH HHS, Id: R01-AI-32177

Mesh Terms

  • Animals
  • Antigens, CD
  • Antigens, CD18
  • Base Sequence
  • Gene Expression
  • Genes
  • Graft Rejection
  • Heart Transplantation
  • Inflammation
  • Mice
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Mutagenesis, Insertional
  • Peritonitis
  • RNA, Messenger
  • Restriction Mapping