Characterization of an exchangeable gene trap using pU‐17 carrying a stop codon‐<i>βgeo</i> cassette

Taniwaki, Takuya; Haruna, Kyoko; Nakamura, Hiroshi; Sekimoto, Tomohisa; Oike, Yuichi; Imaizumi, Tsutomu; Saito, Fumiyo; Muta, Mayumi; Soejima, Yumi; Utoh, Ayako; Nakagata, Naomi; Araki, Masatake; Yamamura, Ken Ichi; Araki, Kimi

doi:10.1111/j.1440-169x.2005.00792.x

Cited by 59 publications

(63 citation statements)

References 38 publications

(56 reference statements)

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“…From this point of view, iPLA 2 ␥ may be responsible for the repair of peroxidized CL in mitochondria. It has been proposed that the consecutive action of PLA 2 and glutathione peroxidase (GPx) is required to reduce lipid peroxides in mitochondria ( 24 ). Like the gene disruption of iPLA 2 ␥ observed in the present study, gene disruption of cGPx, one of the GPx isozymes, has also been shown to result in growth retardation, presumably due in part to mitochondria disorders ( 58 ).…”

Section: Discussionmentioning

confidence: 48%

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Mitochondrial dysfunction and reduced prostaglandin synthesis in skeletal muscle of Group VIB Ca2+-independent phospholipase A2γ-deficient mice

Yoda

Hachisu

Taketomi

et al. 2010

Journal of Lipid Research

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Supplementary key words cardiolipin • mitochondria • muscle • phospholipidsPhospholipase A 2 (PLA 2 ) enzymes catalyze the cleavage of the sn -2 ester bond of glycerophospholipids to yield free fatty acids and lysophospholipids, thereby playing critical roles in cellular lipid metabolisms linked to energy storage, membrane remodeling, and lipid mediator signaling. In the membrane remodeling reaction, fatty acyl groups are fi rst removed (deacylated) by PLA 2 and then replaced (reacylated) with different fatty acyl groups by acyltransferases, which allow membrane phospholipids to acquire a variation of molecular species. In the signaling reaction, polyunsaturated fatty acids [typically arachidonic acid (AA)] and lysophospholipids released by the action of PLA 2 s are metabolized to various lipid mediators, such as prostaglandins (PG), leukotrienes, and platelet-activating factor, which exert a variety of biological actions through their cognate receptors. Abstract Group VIB Ca2+ -independent phospholipase A 2 ␥ (iPLA 2 ␥ ) is a membrane-bound iPLA 2 enzyme with unique features, such as the utilization of distinct translation initiation sites and the presence of mitochondrial and peroxisomal localization signals. Here we investigated the physiological functions of iPLA 2 ␥ by disrupting its gene in mice. iPLA 2 ␥ -knockout (KO) mice were born with an expected Mendelian ratio and appeared normal and healthy at the age of one month but began to show growth retardation from the age of two months as well as kyphosis and significant muscle weakness at the age of four months. Electron microscopy revealed swelling and reduced numbers of mitochondria and atrophy of myofi laments in iPLA 2 ␥ -KO skeletal muscles. Increased lipid peroxidation and the induction of several oxidative stress-related genes were also found in the iPLA 2 ␥ -KO muscles. These results provide evidence that impairment of iPLA 2 ␥ causes mitochondrial dysfunction and increased oxidative stress, leading to the loss of skeletal muscle structure and function. We further found that the compositions of cardiolipin and other phospholipid subclasses were altered and that the levels of myoprotective prostanoids were reduced in iPLA 2 ␥ -KO skeletal muscle. Thus, in addition to maintenance of homeostasis of the mitochondrial membrane, iPLA 2 ␥ may contribute to modulation of lipid mediator production in vivo. -Yoda, E., K. Hachisu, Y. Taketomi, K. Yoshida, M. Nakamura, K. Ikeda, R. Taguchi, Y. Nakatani, H. Kuwata, M. Murakami, I. Kudo, and S. Hara. Mitochondrial dysfunction and reduced prostaglandin synthesis in skeletal muscle of Group VIB Ca 2+ -independent phospholipase A2 ␥ -defi cient mice. J. Lipid Res.

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Section: Discussionmentioning

confidence: 48%

“…The iPLA 2 ␥ gene was disrupted by gene-trapping methods ( 24 ), in which a gene cassette consisting of a splicing acceptor (SA)-␤ geo-pA-pSP73 was integrated between exons 1 and 2 (supplementary Fig. IA).…”

Section: Methodsmentioning

confidence: 99%

Mitochondrial dysfunction and reduced prostaglandin synthesis in skeletal muscle of Group VIB Ca2+-independent phospholipase A2γ-deficient mice

Yoda

Hachisu

Taketomi

et al. 2010

Journal of Lipid Research

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“…A BLAST search using the mouse cDNA sequence identified line Ayu21-18 (15). The description of the generation of Ayu21-18 can be found at http://egtc.jp.…”

Section: Ayu21-18 An Es Cell Line With a Gene-trap Insertion In The mentioning

confidence: 99%

Basonuclin 2 has a function in the multiplication of embryonic craniofacial mesenchymal cells and is orthologous to disco proteins

Vanhoutteghem

Bouche

Delhomme

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Basonuclin 2 is a recently discovered zinc finger protein of unknown function. Its paralog, basonuclin 1, is associated with the ability of keratinocytes to multiply. The basonuclin zinc fingers are closely related to those of the Drosophila proteins disco and discorelated, but the relation between disco proteins and basonuclins has remained elusive because the function of the disco proteins in larval head development seems to have no relation to that of basonuclin 1 and because the amino acid sequence of disco, apart from the zinc fingers, also has no similarity to that of the basonuclins. We have generated mice lacking basonuclin 2. These mice die within 24 h of birth with a cleft palate and abnormalities of craniofacial bones and tongue. In the embryonic head, expression of the basonuclin 2 gene is restricted to mesenchymal cells in the palate, at the periphery of the tongue, and in the mesenchymal sheaths that surround the brain and the osteocartilagineous structures. In late embryos, the rate of multiplication of these mesenchymal cells is greatly diminished. Therefore, basonuclin 2 is essential for the multiplication of craniofacial mesenchymal cells during embryogenesis. Non-Drosophila insect databases available since 2008 reveal that the basonuclins and the disco proteins share much more extensive sequence and gene structure similarity than noted when only Drosophila sequences were examined. We conclude that basonuclin 2 is both structurally and functionally the vertebrate ortholog of the disco proteins. We also note the possibility that some human craniofacial abnormalities are due to a lack of basonuclin 2.cell multiplication ͉ cleft palate

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“…) by gene-trap insertional mutagenesis in embryonic stem cells using an exchangeable trap vector (Taniwaki et al, 2005). Our mutant mice exhibit a milder phenotype than the null mutant mice in terms of their growth and perinatal death rate.…”

Section: Gt/gtmentioning

confidence: 99%

Defective development of the gall bladder and cystic duct in Lgr4‐ hypomorphic mice

Yamashita

Takegawa

Sakumoto

et al. 2009

Developmental Dynamics

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Leucine-rich repeat (LRR) -containing G protein coupled receptor (LGR) family members are characterized by the presence of a seven-transmembrane domain and LRR motifs. We describe a new function for Lgr4 in the development of the gall bladder and cystic duct and in the epithelium-mesenchyme interaction. Lgr4 expression was observed in the gall bladder epithelium when the gall bladder primordium elongated ventrally. Although Lgr4 hypomorphic mutant (Lgr4 Gt/Gt ) embryos developed a normal gall bladder bud at embryonic day (E) 10.25, no further elongation was observed at later stages. At E12.5, the mesenchyme surrounding the gall bladder had completely disappeared in Lgr4Gt/Gt embryos, while the gall bladder remained unelongated. Neighboring tissues such as liver and pancreas were unaffected, as revealed by expression of marker genes. This is the first report of a mutant mouse that lacks a gall bladder and cystic duct without affecting the other tissues that derive from the same hepatic diverticulum. Developmental Dynamics 238:993-1000, 2009.

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Characterization of an exchangeable gene trap using pU‐17 carrying a stop codon‐βgeo cassette

Cited by 59 publications

References 38 publications

Mitochondrial dysfunction and reduced prostaglandin synthesis in skeletal muscle of Group VIB Ca2+-independent phospholipase A2γ-deficient mice

Mitochondrial dysfunction and reduced prostaglandin synthesis in skeletal muscle of Group VIB Ca2+-independent phospholipase A2γ-deficient mice

Basonuclin 2 has a function in the multiplication of embryonic craniofacial mesenchymal cells and is orthologous to disco proteins

Defective development of the gall bladder and cystic duct in Lgr4‐ hypomorphic mice

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