Association of the Gene Encoding Wingless-Type Mammary Tumor Virus Integration-Site Family Member 5B (WNT5B) with Type 2 Diabetes

Abstract Ovarian paracrine mediation by components of the wingless-type mouse mammary tumor virus integration site ligands (WNT1 to 11) and their receptors, Frizzled family members (FZD1 to 10), has been proposed. Secreted truncated forms of FZD proteins (e.g., SFRP4) block the action of WNT ligands. Dickkopf-1 (DKK1) is another WNT antagonist, and R-spondin-1 (RSPO1) is one of a group of four secreted proteins that enhance WNT/β-catenin signaling. Our hypothesis was that granulosa cells signal theca cells (TC) via SFRP4, DKK1, RSPO1 and WNT secretion to regulate TC differentiation and proliferation. Therefore, in vitro experiments were conducted to study the effects of WNT family member 3A (WNT3A), WNT5A, RSPO1, DKK1, insulin-like growth factor 1 (IGF1), bone morphogenetic protein 7 (BMP7), Indian hedgehog (IHH), and fibroblast growth factor-9 (FGF9) on bovine TC proliferation and steroidogenesis. Theca cells of large (8 to 20 mm) and small (3 to 6 mm) follicles were collected from bovine ovaries, TC monolayers were established in vitro, and treated with various doses of recombinant human WNT3A, WNT5A, RSPO1, DKK1, IGF1, FGF9, BMP7, IHH and/or ovine LH in serum-free medium for 48 h. In experiment 1 using LH-treated TC, IGF1, IHH and WNT3A increased (P < 0.05) cell numbers and androstenedione production, whereas WNT3A and BMP7 inhibited (P < 0.05) progesterone production. In experiment 2, FGF9 blocked (P < 0.05) the WNT3A-induced increase in androstenedione production in LH plus IGF1-treated TC. In experiment 3, RSPO1 further increased (P < 0.05) LH plus IGF1-induced progesterone and androstenedione production. In experiment 4, SFRP4 and DKK1 alone had no significant effect on TC proliferation or progesterone production of large-follicle TC, but both blocked the inhibitory effect of WNT5A on androstenedione production. In contrast, DKK1 alone inhibited (P < 0.05) small-follicle TC androstenedione production whereas SFRP4 was without effect. We conclude that the ovarian TC WNT system is functional in cattle, with WNT3A increasing proliferation and androstenedione production of TC.

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Mapping of a mouse mammary tumor virus integration site by retroviral LTR—arbitrary polymerase chain reaction

Virus Research ◽

10.1016/s0168-1702(98)00002-1 ◽

1998 ◽

Vol 54 (2) ◽

pp. 207-215 ◽

Cited By ~ 1

Author(s):

Claus Casper ◽

Christine Leib-Mösch ◽

Brian Salmons ◽

Walter H Günzburg ◽

Gaby Baumann ◽

...

Keyword(s):

Polymerase Chain Reaction ◽

Mouse Mammary Tumor Virus ◽

Integration Site ◽

Chain Reaction ◽

Mammary Tumor Virus ◽

Mouse Mammary Tumor ◽

Tumor Virus ◽

Polymerase Chain ◽

Virus Integration ◽

Virus Integration Site

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Congenital Duplication of the Palm in a Patient with Multiple Anomalies

Journal of Hand Surgery (European Volume) ◽

10.1016/s0266-7681(02)00084-0 ◽

2003 ◽

Vol 28 (3) ◽

pp. 276-279 ◽

Cited By ~ 15

Author(s):

M. M. AL-QATTAN

Keyword(s):

Family Member ◽

Integration Site ◽

Mammary Tumour ◽

Mouse Mammary Tumour Virus ◽

Virus Integration ◽

Virus Integration Site

In 1995, Parr and McMahon described a syndrome of congenital duplication of footpads in mice which lacked a protein called ‘Wingless-type mouse mammary tumour virus integration site family member 7a” (Wnt-7a). This syndrome has not been described in humans and the following report describes a similar syndrome in a Saudi girl. The role of Wnt-7a in the development of the limb along the dorso-ventral axis is discussed, along with interaction between the Wnt-7a and other axes of limb growth.

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Amplification and hormone-regulated expression of a mouse mammary tumor virus-Eco gpt fusion plasmid in mouse 3T6 cells

Molecular and Cellular Biology ◽

10.1128/mcb.3.8.1421-1429.1983 ◽

1983 ◽

Vol 3 (8) ◽

pp. 1421-1429

Author(s):

A B Chapman ◽

M A Costello ◽

F Lee ◽

G M Ringold

Keyword(s):

Mammary Tumor ◽

Mouse Mammary Tumor Virus ◽

Glucocorticoid Receptors ◽

Gene Encoding ◽

Mammary Tumor Virus ◽

General Utility ◽

Mouse Mammary Tumor ◽

Tumor Virus ◽

Mmtv Promoter ◽

Low Levels

Mouse 3T6 cells were transformed with a chimeric DNA plasmid, pSVMgpt, in which the mouse mammary tumor virus (MMTV) promoter was fused to the Escherichia coli gene encoding xanthine-guanine phosphoribosyl transferase (Eco gpt). The transformants exhibited glucocorticoid-inducible expression of Eco gpt. With limiting xanthine concentrations, conditions were established in which cell growth became hormone dependent. Cells selected for their ability to grow in limiting concentrations of both xanthine and glucocorticoids contained amplified levels of Eco gpt DNA, and expression of Eco gpt remained glucocorticoid inducible in these amplified cells. Thus, amplification of the MMTV promoter region in itself did not abolish hormonal responsiveness of a gene. In addition to increased levels of Eco gpt DNA, some of the selected cells also exhibited increased levels (two- to threefold) of glucocorticoid receptors. Lastly, we found that excessive expression of Eco gpt is toxic to 3T6 cells; by maintaining low hormone levels and, therefore, low levels of expression, we were able to select cells with amplified Eco gpt. Thus, the MMTV promoter may be of general utility in expressing genes whose products may be lethal if they are produced in excessive quantities.

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