The hippocampal neurons of neuronal apoptosis inhibitory protein 1 (NAIP1)-deleted mice display increased vulnerability to kainic acid-induced injury

The hippocampal neurons of neuronal apoptosis inhibitory protein 1 (NAIP1)-deleted mice display increased vulnerability to kainic acid-induced injury

^*Solange Gauthier Karsh Molecular Genetics Laboratory, Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON Canada K1H 8L1; and ^§Department of Biochemistry, Microbiology, and Immunology, and ^†Apoptogen Incorporated, University of Ottawa, Ottawa, ON Canada K1H 8M5

Edited by W. Maxwell Cowan, Howard Hughes Medical Institute, Chevy Chase, MD, and approved December 17, 1999 (received for review October 29, 1999)

Abstract

The neuronal apoptosis inhibitory protein (NAIP) is a member of a novel family of inhibitor of apoptosis (IAP) proteins. The IAP genes are highly conserved from baculovirus to metazoans and suppress apoptosis induced by a variety of triggers both in vitro and in vivo. Here we describe the generation and characterization of mice with the targeted deletion of NAIP1. We demonstrate that the NAIP1-deleted mice develop normally. However, the survival of pyramidal neurons in the hippocampus after kainic acid-induced limbic seizures is greatly reduced in the NAIP1 knock-out animals. Thus, although NAIP1 is not necessary for normal development of murine central nervous system, the endogenous NAIP1 is required for neuronal survival in pathological conditions.

Footnotes

↵ ‡ To whom reprint requests should be addressed. E-mail: alex{at}mgcheo.med.uottawa.ca.
This paper was submitted directly (Track II) to the PNAS office.
Article published online before print: Proc. Natl. Acad. Sci. USA, 10.1073/pnas.040469797.
Article and publication date are at www.pnas.org/cgi/doi/10.1073/pnas.040469797
Abbreviations:

NAIP,

neuronal apoptosis inhibitory protein;

ISEL,

in situ end labeling;

KA,

kainic acid;

BIR,

baculoviral inhibitor of apoptosis repeat;

IAP,

inhibitor of apoptosis;

CNS,

central nervous system;

SMA,

spinal muscular atrophy