Genetic regulation of lipopolysaccharide responses in NZB mice

E. A. Bearer, A. A. Ansari, M. Eric Gershwin

Research output: Contribution to journalArticle

Abstract

Several of the autoimmune defects of NZB mice have been linked to chromosome 4 where the Lps gene which regulates B cell activation by bacterial lipopolysaccharide (LPS) is found. Thus, studies of an NZB·Lps(d) strain may facilitate functional analysis of B cell hyperactivity. To develop NZB·Lps(d) mice, the Lps(d) mutation of C57BL/10ScN mice was further characterized by studying the influence of Lps(d) on LPS-induced spleen cell proliferation colony-stimulating factor (CSF) production, and B cell colony-forming unit (CFU-B) proliferation in (C57BL/10SnJ x C57BL/10ScN) F1 x C57BL/10ScN mice. Twenty-one of 27 backcross offspring demonstrated concordance of results in the three assays indicating common genetic regulation of these traits. Subsequently, the Lps allele of NZB mice was characterized by determining the mitogen responsiveness, CSF production and CFU-B proliferation of (NZB x C57BL/10ScN) F1 x C57BL/10ScN mice. In addition, concordance of assortment of the C57BL/10ScN Mupb allele and LPS unresponsiveness was verified. Results of these assays were concordant in 12 of 14 backcross mice, indicating that NZB LPS responsiveness is also regulated by a gene or closely linked set of genes on chromosome 4. Further, the LPS responsiveness of homozygous fifth backcross NZB·Lps(d) mice was significantly diminished compared to that of NZB mice. Interestingly, the hypergammaglobulinemia and anti-DNA antibody levels in 6-month-old Lps(d) mice did not differ from those of NZB mice despite the absence of LPS-responsive CFU-B.

Original languageEnglish (US)
Pages (from-to)193-203
Number of pages11
JournalExperimental and Clinical Immunogenetics
Volume6
Issue number3
StatePublished - 1989

Fingerprint

Inbred NZB Mouse
Lipopolysaccharides
Inbred C57BL Mouse
Colony-Stimulating Factors
Chromosomes, Human, Pair 4
B-Lymphocytes
Alleles
Genes
Hypergammaglobulinemia
Antinuclear Antibodies
Mitogens
Stem Cells
Spleen
Cell Proliferation
Mutation

ASJC Scopus subject areas

  • Genetics
  • Immunology
  • Genetics(clinical)

Cite this

Genetic regulation of lipopolysaccharide responses in NZB mice. / Bearer, E. A.; Ansari, A. A.; Gershwin, M. Eric.

In: Experimental and Clinical Immunogenetics, Vol. 6, No. 3, 1989, p. 193-203.

Research output: Contribution to journalArticle

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