Characterization of lpa2 (Edg4) and lpa1/lpa2 (Edg2/Edg4) lysophosphatidic acid receptor knockout mice: Signaling deficits without obvious phenotypic abnormality attributable to lpa2

James J A Contos, Isao Ishii, Nobuyuki Fukushima, Marcy A. Kingsbury, Xiaoqin Ye, Shuji Kawamura, Joan Heller Brown, Jerold Chun

Research output: Contribution to journalArticle

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Abstract

Lysophosphatidic acid (LPA), a bioactive lipid produced by several cell types including postmitotic neurons and activated platelets, is thought to be involved in various biological processes, including brain development. Three cognate G protein-coupled receptors encoded by lpa1/lpA1/Edg-2/Gpcr26, lpa2/lpA2/Edg-4, and lpa3/lpA3/ Edg-7 mediate the cellular effects of LPA. We have previously shown that deletion of lpa1 in mice results in craniofacial dysmorphism, semilethality due to defective suckling behavior, and generation of a small fraction of pups with frontal hematoma. To further investigate the role of these receptors and LPA signaling in the organism, we deleted lpa2 in mice. Homozygous knockout (lpa2 (-/-)) mice were born at the expected frequency and displayed no obvious phenotypic abnormalities. Intercrosses allowed generation of lpa1 (-/-) lpa2 (-/-) double knockout mice, which displayed no additional phenotypic abnormalities relative to lpa1 (-/-) mice except for an increased incidence of perinatal frontal hematoma. Histological analyses of lpa1 (-/-) lpa2 (-/-) embryonic cerebral cortices did not reveal obvious differences in the proliferating cell population. However, many LPA-induced responses, including phospholipase C activation, Ca2+ mobilization, adenylyl cyclase activation, proliferation, JNK activation, Akt activation, and stress fiber formation, were absent or severely reduced in embryonic fibroblasts derived from lpa1 (-/-) lpa2 (-/-) mice. Except for adenylyl cyclase activation [which was nearly abolished in lpa1 (-/-) fibroblasts], these responses were only partially affected in lpa1 (-/-) and lpa2 (-/-) fibroblasts. Thus, although LPA2 is not essential for normal mouse development, it does act redundantly with LPA1 to mediate most LPA responses in fibroblasts.

Original languageEnglish
Pages (from-to)6921-6929
Number of pages9
JournalMolecular and Cellular Biology
Volume22
Issue number19
DOIs
Publication statusPublished - 2002 Oct
Externally publishedYes

Fingerprint

Lysophosphatidic Acid Receptors
Knockout Mice
Fibroblasts
Adenylyl Cyclases
Hematoma
Biological Phenomena
Stress Fibers
Type C Phospholipases
G-Protein-Coupled Receptors
Cerebral Cortex
Blood Platelets
Lipids
Neurons
lysophosphatidic acid
Incidence
Brain
Population

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Characterization of lpa2 (Edg4) and lpa1/lpa2 (Edg2/Edg4) lysophosphatidic acid receptor knockout mice : Signaling deficits without obvious phenotypic abnormality attributable to lpa2. / Contos, James J A; Ishii, Isao; Fukushima, Nobuyuki; Kingsbury, Marcy A.; Ye, Xiaoqin; Kawamura, Shuji; Brown, Joan Heller; Chun, Jerold.

In: Molecular and Cellular Biology, Vol. 22, No. 19, 10.2002, p. 6921-6929.

Research output: Contribution to journalArticle

Contos, James J A ; Ishii, Isao ; Fukushima, Nobuyuki ; Kingsbury, Marcy A. ; Ye, Xiaoqin ; Kawamura, Shuji ; Brown, Joan Heller ; Chun, Jerold. / Characterization of lpa2 (Edg4) and lpa1/lpa2 (Edg2/Edg4) lysophosphatidic acid receptor knockout mice : Signaling deficits without obvious phenotypic abnormality attributable to lpa2. In: Molecular and Cellular Biology. 2002 ; Vol. 22, No. 19. pp. 6921-6929.
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abstract = "Lysophosphatidic acid (LPA), a bioactive lipid produced by several cell types including postmitotic neurons and activated platelets, is thought to be involved in various biological processes, including brain development. Three cognate G protein-coupled receptors encoded by lpa1/lpA1/Edg-2/Gpcr26, lpa2/lpA2/Edg-4, and lpa3/lpA3/ Edg-7 mediate the cellular effects of LPA. We have previously shown that deletion of lpa1 in mice results in craniofacial dysmorphism, semilethality due to defective suckling behavior, and generation of a small fraction of pups with frontal hematoma. To further investigate the role of these receptors and LPA signaling in the organism, we deleted lpa2 in mice. Homozygous knockout (lpa2 (-/-)) mice were born at the expected frequency and displayed no obvious phenotypic abnormalities. Intercrosses allowed generation of lpa1 (-/-) lpa2 (-/-) double knockout mice, which displayed no additional phenotypic abnormalities relative to lpa1 (-/-) mice except for an increased incidence of perinatal frontal hematoma. Histological analyses of lpa1 (-/-) lpa2 (-/-) embryonic cerebral cortices did not reveal obvious differences in the proliferating cell population. However, many LPA-induced responses, including phospholipase C activation, Ca2+ mobilization, adenylyl cyclase activation, proliferation, JNK activation, Akt activation, and stress fiber formation, were absent or severely reduced in embryonic fibroblasts derived from lpa1 (-/-) lpa2 (-/-) mice. Except for adenylyl cyclase activation [which was nearly abolished in lpa1 (-/-) fibroblasts], these responses were only partially affected in lpa1 (-/-) and lpa2 (-/-) fibroblasts. Thus, although LPA2 is not essential for normal mouse development, it does act redundantly with LPA1 to mediate most LPA responses in fibroblasts.",
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AU - Ishii, Isao

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AU - Kawamura, Shuji

AU - Brown, Joan Heller

AU - Chun, Jerold

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