| Gene Summary for NIH-1841 |
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| Functional Category: |
enzyme-phosphodiesterase |
| Cell Location: |
extracellular |
| OST/GST: |
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| Mouse Nucleotide Accession #: |
NM_015744 |
| Human Nucleotide Accession #: |
NM_006209 |
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| Summary: |
| The gene of interest is mouse Enpp2 (ectonucleotide pyrophosphatase/phosphodiesterase 2), ortholog of human ENPP2. Aliases include ATX, Npps2, Autotaxin, NPP2, ATX-X, PDNP2, LysoPLD, FLJ26803, and PD-IALPHA. ENPP2 is a secreted enzyme that primarily catalyzes the hydrolysis of lysophosphatidylcholine to form lysophosphatidic acid (LPA) (Koike et al, 2006; Xie and Meier, 2004). The enzyme is also capable of catalyzing the hydrolysis of sphingosylphosphoryl choline to form sphingosine 1-phosphate (S1P) (Dennis et al, 2005; van Meeteren et al, 2005). Both LPA and S1P function as lipid mediators that bind with and activate specific G protein-coupled receptors (Ishii et al, 2004). ENPP2 likely plays a role in processes such as neurogenesis, oligodendrocyte differentiation, myelination (van Meeteren et al, 2005), angiogenesis, metastasis (van Meeteren et al, 2006), apoptosis (Song et al, 2005), adipocyte insulin resistance (Boucher et al, 2005), glioblastoma cell migration (Kishi et al, 2006), and keratinocyte cell migration (Mazereeuw-Hautier et al, 2005). Van Meeteren and colleagues (2006) investigated the physiological role of ENPP2 using knockout mice. They showed that ENPP2 homozygous null mice die at embryonic day 9.5, displaying profound vascular defects in the embryo and yolk sac. They also showed that ENPP2 homozygous null mice display allantois malformation, neural tube defects, and asymmetric head folds at embryonic day 8.5. Van Meeteren and colleagues concluded that ENPP2 is the major LPA-producing enzyme and that ENPP2 plays an important role in blood vessel formation during development. |
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| Phenotypic Summary for NIH-1841 |
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Genetic data indicate that this mutation resulted in lethality of the homozygous mutants. The heterozygous mice exhibited a decreased median serum IL-6 response and slightly decreased median TNF-alpha and MCP-1 responses to LPS challenge when compared with their wild-type littermates and the historical mean. Disruption of the target gene was confirmed by Southern hybridization analysis. |
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| Genetics project Specific Summary : NIH-1841 |
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| Mouse Gene Sequence Information |
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Nucleotide Reference: |
NM_015744 ACCESSION:NM_015744 NID: gi 7657450 ref NM_015744.1 Mus musculus ectonucleotide pyrophosphatase/phosphodiesterase 2 (Enpp2), mRNA |
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Protein Reference: |
Q9R1E6 ACCESSION:Q9R1E6 NID: Mus musculus (Mouse). Ectonucleotide pyrophosphatase/phosphodiesterase 2 (E-NPP 2) (Phosphodiesterase I/nucleotide pyrophosphatase 2) (Phosphodiesterase I alpha) (PD-Ialpha) [Includes: Alkaline phosphodiesterase I (EC 3.1.4.1); Nucleotide pyrophosphatase (EC 3.6.1.9) (NPPase)]. MOUSESPTRNRDB |
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Entrez Gene: |
18606 |
| Human Gene Sequence Information |
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Nucleotide Reference: |
NM_006209 ACCESSION:NM_006209 NID: gi 20070229 ref NM_006209.2 Homo sapiens ectonucleotide pyrophosphatase/phosphodiesterase 2 (autotaxin) (ENPP2), mRNA |
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Protein Reference: |
Q13822 ACCESSION:Q13822 NID: Homo sapiens (Human). AUTOTAXIN-T. HUMANSPTRNRDB |
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Entrez Gene: |
5168 |
| Bibliographic References |
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| Title |
Autotaxin, a secreted lysophospholipase D, is essential for blood vessel formation during development. |
| Author[s] |
van Meeteren Laurens A, Ruurs Paula, Stortelers Catelijne, Bouwman Peter, van Rooijen Marga A, Pradère Jean Philippe, Pettit Trevor R, Wakelam Michael J O, Saulnier-Blache Jean Sébastien, Mummery Christine L, Moolenaar Wouter H, Jonkers Jos |
| Journal |
Mol Cell Biol. 07/01/2006; 26:5015-22 |
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| Title |
Autotaxin (lysoPLD/NPP2) protects fibroblasts from apoptosis through its enzymatic product, lysophosphatidic acid, utilizing albumin-bound substrate. |
| Author[s] |
Song Jaehwi, Clair Timothy, Noh Ji Heon, Eun Jung Woo, Ryu So Yeon, Lee Shi Nae, Ahn Young Min, Kim Su Young, Lee Sug Hyung, Park Won Sang, Yoo Nam Jin, Lee Jung Young, Nam Suk Woo |
| Journal |
Biochem Biophys Res Commun. 11/25/2005; 337:967-75 |
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| Title |
Potential involvement of adipocyte insulin resistance in obesity-associated up-regulation of adipocyte lysophospholipase D/autotaxin expression. |
| Author[s] |
Boucher J, Quilliot D, Pradères J P, Simon M F, Grès S, Guigné C, Prévot D, Ferry G, Boutin J A, Carpéné C, Valet P, Saulnier-Blache J S |
| Journal |
Diabetologia. 03/01/2005; 48:569-77 |
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| Mutation Information |
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| Mutation Type: |
Homologous Recombination (standard) |
| Description: |
The gene consists of 25 exons, with the start codon located in exon 1 (NCBI accession NM_015744.1). Exons 1 and 2 were targeted. |
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