An attempt to develop mouse model for anti-laminin γ1 pemphigoid.

Abstract

BACKGROUND:

We recently reported that the autoantibodies of anti-p200 pemphigoid sera react with laminin γ1 and renamed this entity as anti-laminin γ1 pemphigoid. However, it has not been clarified whether the anti-laminin γ1 autoantibodies, particularly those to the C-terminal integrin binding site, affect the dermoepidermal junction and cause subepidermal blisters.

OBJECTIVE:

The aim of this study was to develop animal models for anti-laminin γ1 pemphigoid.

METHODS:

We attempted to produce two mouse models for anti-laminin γ1 pemphigoid; (1) a passive transfer model: injection of rabbit IgG to shorter bacterial recombinant protein of the murine laminin γ1 C-terminal 107 amino acids, and (2) an active disease model: direct immunization to mice with this recombinant protein.

RESULTS:

Immunoblotting revealed that 70% of patient sera reacted with the shorter recombinant protein of human laminin γ1 C-terminus. In the passive transfer model, rabbit IgG to the murine laminin γ1 C-terminus was deposited, without C3 deposition, at the epidermal basement membrane zone. In contrast, in the active disease model, direct immunofluorescence of mouse skin sections showed no deposition of either murine IgG or C3. Blister formation was not seen in either model both phenotypically and histopathologically.

CONCLUSION:

In the two different mouse animal models for anti-laminin γ1 pemphigoid, although rabbit IgG to the recombinant laminin γ1 C-terminus bound to the epidermal basement membrane zone in passive transfer model, no obvious blister formation was seen. To reproduce skin lesions in mouse models for anti-laminin γ1 pemphigoid, further improvement should be needed.

• Authors: Hiroshi Koga, Norito Ishii, Teruki Dainichi, Daisuke Tsuruta, Takahiro Hamada, Chika Ohata, Tadashi Karashima, Minao Furumura, Takashi Hashimoto
• Journal: Journal of dermatological science (J Dermatol Sci) Vol. 70 Issue 2 Pg. 108-15 (May 2013) ISSN: 1873-569X [Electronic] Netherlands
• PMID: 23410740 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Amino Acids
• Autoantibodies
• Immunoglobulin G
• Laminin
• Recombinant Proteins
• laminin gamma 1

Topics

• Amino Acids (immunology)
• Animals
• Autoantibodies (immunology)
• Disease Models, Animal
• Humans
• Immunity, Active (immunology)
• Immunization, Passive
• Immunoglobulin G (immunology)
• Laminin (immunology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Pemphigoid, Bullous (immunology)
• Rabbits
• Recombinant Proteins (immunology)