Disease relevance of Naip1

• Thus, unregulation of cellular differentiation and/or caspase suppression may contribute to motoneuron dysfunction and cell death in spinal muscular atrophy where NAIP is mutated [1].
• NAIP, c-IAP1 (inhibitor of apoptosis-1), c-IAP2, X-IAP, survivin and Apollon comprise the mammalian inhibitors of the apoptosis family and contain an N-terminal domain with 1-3 imperfect repeats of an approximately 65 amino acids domain named the baculovirus IAP repeat (BIR) motif [1].
• Furthermore, we have investigated the effects of NAIP in the rat pheochromocytoma PC12 cell line [1].
• Prior genetic and physical mapping has shown that the Naip gene cluster on mouse chromosome 13D1-D3 contains a gene, Lgn1, that is responsible for determining the permissivity of ex vivo macrophages to Legionella pneumophila replication [2].
• The human neuronal apoptosis inhibitory protein (NAIP) gene was originally discovered because of its deletion in infantile spinal muscular atrophy (SMA), a childhood genetic disorder characterized by motor neuron loss and progressive paralysis with muscular atrophy [3].

Psychiatry related information on Naip1

• We have identified differences in the structure of the Naip array among commonly used inbred mouse strains, although these gross structural differences do not correlate with differences in L. pneumophila permissiveness [2].

High impact information on Naip1

• In inbred mouse strains, permissiveness to intracellular replication of Legionella pneumophila is controlled by a single locus (Lgn1), which maps to a region within distal Chromosome 13 that contains multiple copies of the gene baculoviral IAP repeat-containing 1 (Birc1, also called Naip; refs. 1-3) [4].
• The neuronal apoptosis inhibitory protein (NAIP) is a member of a novel family of inhibitor of apoptosis (IAP) proteins [5].
• The hippocampal neurons of neuronal apoptosis inhibitory protein 1 (NAIP1)-deleted mice display increased vulnerability to kainic acid-induced injury [5].
• 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 [5].
• However, the survival of pyramidal neurons in the hippocampus after kainic acid-induced limbic seizures is greatly reduced in the NAIP1 knock-out animals [5].

Biological context of Naip1

• In order to gather more information about polymorphisms among the Naip genes of the 129 mouse haplotype, we have determined the genomic sequence of a substantial portion of the 129 Naip gene array [6].
• The only regional candidate genes for this phenotype difference lie within a cluster of closely linked paralogs of the Neuronal Apoptosis Inhibitory Protein (Naip) gene [6].
• The neuronal apoptosis inhibitory protein suppresses neuronal differentiation and apoptosis in PC12 cells [1].
• Expression of full-length but not BIR-deleted-NAIP protects against cell death [1].
• We identified six NAIP genes in the mouse genome which were found to be expressed in a broad range of tissues [1].

Anatomical context of Naip1

• The human neuronal apoptosis inhibitory protein (NAIP) gene has been discovered as a candidate gene for spinal muscular atrophy, a genetic disorder characterized by motor neuron loss in the spinal cord [1].
• We observed that NAIP overexpression impaired NGF-induced neurite outgrowth [1].
• Immunoblotting and immunoprecipitation analyses identify Naip protein expression in mouse macrophages and in macrophage cell lines RAW 264.7 and J774A [7].
• At E16.5, NAIP mRNA transcripts were found in the marginal zone of the lateral ventricle, the follicles of the vibrissae, in the retina and in the intestinal villi [8].
• Expression and regulation of neuronal apoptosis inhibitory protein during adipocyte differentiation [9].

Associations of Naip1 with chemical compounds

• Likewise, an increase in Naip protein levels in macrophages is observed 24 h after phagocytosis of Latex beads [7].
• In 3T3-L1 cells, the increase in NAIP occurred by day 4 of the 8-day differentiation protocol, which includes exposure of confluent preadipocytes to insulin, dexamethasone, and isobutylmethylxanthine [9].
• These observations suggest that the powerful effects of PAX2 on renal branching morphogenesis and final nephron number may be mediated by activation of Naip which then suppresses apoptosis in UB cells [10].

Other interactions of Naip1

• This model predicts the presence of two distinct families of Naip paralogs: Naip1/2/3 and Naip4/5/6/7 [6].
• Here we present the cloning and characterization of multiple copies of the mouse homologue of NAIP, Naip1-Naip6 [11].
• However, the BIR domains of NAIP were essential to prevent apoptosis in PC12 cells after NGF deprivation or TNF-alpha receptor stimulation [1].
• Two candidate genes-survival motor neuron (SMN) and neuronal apoptosis inhibitory protein have been identified on chromosome 5q13 by positional cloning [12].
• To date, many treatment strategies have been developed for cerebral ischemia using target genes such as neuronal apoptosis inhibitory protein (NAIP), glial cell line-derived neurotrophic factor (GDNF), sensitive to apoptosis gene (SAG), 150-kDa oxygen-regulated protein (ORP150), etc [13].

Analytical, diagnostic and therapeutic context of Naip1

• Genomic sequence analysis of the mouse Naip gene array [6].
• NAIP mRNA is present in the developing brain and spinal cord of E9.5-E14.5 mouse embryos as detected by various in situ hybridization techniques [8].

References