A novel mouse model for the hyper-IgM syndrome

A spontaneous activation-induced cytidine deaminase mutation leading to complete loss of Ig class switching and reduced somatic hypermutation

Carin I M Dahlberg, Minghui He, Torkild Visnes, Magda Liz Torres, Elena M. Cortizas, Ramiro E Verdun, Lisa S. Westerberg, Eva Severinson, Lena Ström

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

We describe a spontaneously derived mouse line that completely failed to induce Ig class switching in vitro and in vivo. The mice inherited abolished IgG serum titers in a recessive manner caused by a spontaneous G→A transition mutation in codon 112 of the aicda gene, leading to an arginine to histidine replacement (AIDR112H). Ig class switching was completely reconstituted by expressing wild-type AID. Mice homozygous for AIDR112H had peripheral B cell hyperplasia and large germinal centers in the absence of Ag challenge. Immunization with SRBCs elicited an Ag-specific IgG1 response in wild-type mice, whereas AIDR112H mice failed to produce IgG1 and had reduced somatic hypermutation. The phenotype recapitulates the human hyper-IgM (HIGM) syndrome that is caused by point mutations in the orthologous gene in humans, and the AIDR112H mutation is frequently found in HIGM patients. The AIDR112H mouse model for HIGM provides a powerful and more precise tool than conventional knockout strategies.

Original languageEnglish
Pages (from-to)4732-4738
Number of pages7
JournalJournal of Immunology
Volume193
Issue number9
DOIs
StatePublished - Jan 1 2014

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Hyper-IgM Immunodeficiency Syndrome
Immunoglobulin Class Switching
Mutation
Immunoglobulin G
Immunoglobulin M
Germinal Center
Point Mutation
Histidine
Codon
Genes
Hyperplasia
Arginine
AICDA (activation-induced cytidine deaminase)
Immunization
B-Lymphocytes
Phenotype

ASJC Scopus subject areas

  • Immunology

Cite this

A novel mouse model for the hyper-IgM syndrome : A spontaneous activation-induced cytidine deaminase mutation leading to complete loss of Ig class switching and reduced somatic hypermutation. / Dahlberg, Carin I M; He, Minghui; Visnes, Torkild; Torres, Magda Liz; Cortizas, Elena M.; Verdun, Ramiro E; Westerberg, Lisa S.; Severinson, Eva; Ström, Lena.

In: Journal of Immunology, Vol. 193, No. 9, 01.01.2014, p. 4732-4738.

Research output: Contribution to journalArticle

Dahlberg, Carin I M ; He, Minghui ; Visnes, Torkild ; Torres, Magda Liz ; Cortizas, Elena M. ; Verdun, Ramiro E ; Westerberg, Lisa S. ; Severinson, Eva ; Ström, Lena. / A novel mouse model for the hyper-IgM syndrome : A spontaneous activation-induced cytidine deaminase mutation leading to complete loss of Ig class switching and reduced somatic hypermutation. In: Journal of Immunology. 2014 ; Vol. 193, No. 9. pp. 4732-4738.
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