Genetic and functional evaluation of the level of inbreeding of the Westran pig: a herd with potential for use in xenotransplantation.

Abstract:

BACKGROUND:The Westran pig has been purposely inbred for use in xenotransplantation. The herd originated in the wild from a limited gene pool and has been inbred by repeated full-sib matings for nine generations. METHODS:The aim of this study was to evaluate the level of inbreeding by functional assays, such as bi-directional MLR and reciprocal skin grafts between herd members, and by genetic analysis using highly polymorphic genetic markers to calculate the level of inbreeding. RESULTS:The MLR between herd members were non-reactive whereas there was a prompt response to third party pig lymphocytes, indicative of a normal immune responsiveness in Westran pigs but isogenicity of the major histocompatibility complex. Skin grafts between male siblings or female sibling skin grafts on male recipients showed prolonged survival but with few exceptions did not survive beyond 100 days suggesting that by the fifth generation the Westran herd was still mismatched at minor histocompatibility antigens. This level of functional inbreeding was confirmed by microsatellite analysis of highly polymorphic markers, which showed that 52 of 53 chromosomally dispersed markers were fixed by the ninth generation. This level of fixation was consistent with 19 to 20 generations of full-sibling inbreeding. The calculated inbreeding coefficient at generation 10 was 0.98159. CONCLUSIONS:This analysis confirms that the Westran pig is highly inbred and we propose that analysis of chromosomally dispersed highly polymorphic markers is an accurate and reproducible method for assessing the level of inbreeding of a pig herd.

journal_name

Xenotransplantation

journal_title

Xenotransplantation

authors

O'Connell PJ,Hawthorne WJ,Simond D,Chapman JR,Chen Y,Patel AT,Walters SN,Burgess J,Weston L,Stokes RA,Moran C,Allen R

doi

10.1111/j.1399-3089.2005.00230.x

subject

Has Abstract

pub_date

2005-07-01 00:00:00

pages

308-15

issue

4

eissn

0908-665X

issn

1399-3089

pii

XEN230

journal_volume

12

pub_type

杂志文章
  • Xenotransfusions, past and present.

    abstract::The first blood transfusions in humans were xenotransfusions, carried out by Jean-Baptiste Denis beginning in 1667. Richard Lower, Matthäus Purmann and Georges Mercklin also experimented with the use of animal blood for transfusion until this practice was forbidden in 1670, after the death of one of Denis's patients. ...

    journal_title:Xenotransplantation

    pub_type: 历史文章,杂志文章

    doi:10.1111/j.1399-3089.2007.00404.x

    authors: Roux FA,Saï P,Deschamps JY

    更新日期:2007-05-01 00:00:00

  • Anti-Gal antibody-mediated skin graft rejection requires a threshold level of Gal expression.

    abstract:BACKGROUND:Despite overcoming xenograft hyperacute rejection (HAR), Gal (galactose-alpha1,3-galactose) expression may not be completely eliminated from the alpha1,3-galactosyltransferase gene knockout (Gal KO) pig because of alternative galactosyltransferases. Whether low levels of "residual" Gal are still susceptible ...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/j.1399-3089.2007.00437.x

    authors: Murray-Segal L,Gock H,Cowan PJ,d'Apice AJ

    更新日期:2008-02-01 00:00:00

  • Intragraft cytokine mRNA expression in rejecting and non-rejecting vascularized xenografts.

    abstract:BACKGROUND:The aim of the present study was to further investigate the characteristics of both graft-infiltrating cells and splenocytes during acute vascular rejection (AVR), cell-mediated rejection and non-rejection of vascularized concordant xenografts, by analysing both proinflammatory [interleukin-1beta (IL-1beta) ...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1034/j.1399-3089.2003.02032.x

    authors: Lorant T,Krook H,Wilton J,Olausson M,Tufveson G,Korsgren O,Johnsson C

    更新日期:2003-07-01 00:00:00

  • Initial experience with the human anti-human CD154 monoclonal antibody, ABI793, in pig-to-baboon xenotransplantation.

    abstract:BACKGROUND:ABI793 (ABI) is a human monoclonal antibody (mAb) specific for human CD154. To assess the suitability of ABI for baboon transplantation studies, we carried out in vitro studies to determine ABI's reactivity with baboon cells expressing CD154, performed in vivo pharmacokinetic studies in two baboons, and test...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/j.1399-3089.2004.00148.x

    authors: Knosalla C,Ryan DJ,Moran K,Gollackner B,Schuler W,Sachs DH,Awwad M,Schuurman HJ,Cooper DK

    更新日期:2004-07-01 00:00:00

  • T-cell-mediated immunological barriers to xenotransplantation.

    abstract::Xenotransplantion remains the most viable option for significant expansion of the donor organ pool in clinical transplantation. With the advent of nuclear transfer technologies, the production of transgenic swine has become a possibility. These animals have allowed transplant investigators to overcome humoral mechanis...

    journal_title:Xenotransplantation

    pub_type: 杂志文章,评审

    doi:10.1111/j.1399-3089.2011.00687.x

    authors: Scalea J,Hanecamp I,Robson SC,Yamada K

    更新日期:2012-01-01 00:00:00

  • Rat-to-mouse small bowel xenotransplantation: a novel model for studying acute vascular and hyperacute xenograft rejection and xenogenic cell migration.

    abstract::The present study was undertaken to establish a rat-to-mouse vascularized small bowel xenotransplantation model to study acute vascular and hyperacute xenograft rejection, and xenogenic cell migration. Lewis rat small bowel grafts were transplanted heterotopically to group 1, Balb/c mice, and group 2, Balb/c mice pre-...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1034/j.1399-3089.1999.00001.x

    authors: Kiyochi H,Kellersmann R,Blömer A,Garcia BM,Zhang Z,Zhong R,Grant DR

    更新日期:1999-02-01 00:00:00

  • Impaired spinal cord remyelination by long-term cultured adult porcine olfactory ensheathing cells correlates with altered in vitro phenotypic properties.

    abstract:BACKGROUND:Extensive studies in rodents have identified olfactory ensheathing cells (OECs) as promising candidates for cell-based therapies of spinal cord and peripheral nerve injury. Previously, we demonstrated that short-term cultured adult porcine OECs can remyelinate the rodent and non-human primate spinal cord. He...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/j.1399-3089.2009.00562.x

    authors: Radtke C,Lankford KL,Wewetzer K,Imaizumi T,Fodor WL,Kocsis JD

    更新日期:2010-01-01 00:00:00

  • Detection of Hanganutziu-Deicher antigens in O-glycans from pig heart tissues by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

    abstract:BACKGROUND:In the α1,3-galactosyltransferase knockout (α-GalT KO) pig era, identification of the non-Gal epitopes is necessary for successful pig-to-human xenotransplantation. Recently, we successfully detected α-Gal epitopes as well as Hanganutziu-Deicher (H-D) antigens from the N-glycans in the pig heart tissues, whi...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/xen.12045

    authors: Jeong HJ,Adhya M,Park HM,Kim YG,Kim BG

    更新日期:2013-11-01 00:00:00

  • Islet cell xenotransplantation: a serious look toward the clinic.

    abstract::Type I diabetes remains a significant clinical problem in need of a reliable, generally applicable solution. Both whole organ pancreas and islet allotransplantation have been shown to grant patients insulin independence, but organ availability has restricted these procedures to an exceptionally small subset of the dia...

    journal_title:Xenotransplantation

    pub_type: 杂志文章,评审

    doi:10.1111/xen.12095

    authors: Samy KP,Martin BM,Turgeon NA,Kirk AD

    更新日期:2014-05-01 00:00:00

  • Diabetes induction by total pancreatectomy in minipigs with simultaneous splenectomy: a feasible approach for advanced diabetes research.

    abstract:BACKGROUND:Safe and reliable diabetes models are a key prerequisite for advanced preclinical studies on diabetes. Chemical induction is the standard model of diabetes in rodents and also widely used in large animal models of non-human primates and minipigs. However, uncertain efficacy, the potential of beta-cell regene...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/xen.12255

    authors: Heinke S,Ludwig B,Schubert U,Schmid J,Kiss T,Steffen A,Bornstein S,Ludwig S

    更新日期:2016-09-01 00:00:00

  • Regulation of xenogeneic porcine pancreatic islets.

    abstract::The use of xenogeneic porcine pancreatic islets has been shown to be a potentially promising alternative to using human allogeneic islets to treat insulin-dependent type 1 diabetes (T1D). This article provides an overview of the existing FDA regulatory framework that would be applied to the regulation of clinical tria...

    journal_title:Xenotransplantation

    pub_type: 杂志文章,评审

    doi:10.1111/j.1399-3089.2010.00592.x

    authors: Arcidiacono JA,Evdokimov E,Lee MH,Jones J,Rudenko L,Schneider B,Snoy PJ,Wei CH,Wensky AK,Wonnacott K

    更新日期:2010-09-01 00:00:00

  • The distribution of porcine pancreatic beta-cells at ages 5, 12 and 24 weeks.

    abstract::Islet transplantation is a potential treatment for diabetes mellitus and porcine pancreata may provide a readily available source of islets. The size, number and distribution of islets within the pancreas may influence the choice of age of donor for xenotransplantation. Samples (n = 3 per age group) from the dorsal an...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1034/j.1399-3089.1999.00009.x

    authors: Jay TR,Heald KA,Carless NJ,Topham DE,Downing R

    更新日期:1999-05-01 00:00:00

  • Pig islet xenografts are resistant to autoimmune destruction by non-obese diabetic recipients after anti-CD4 treatment.

    abstract::In addition to providing a large source of donor tissue, xenogeneic islet transplantation might avoid recurrent autoimmunity in patients with type 1 diabetes. To examine this possibility further, xenogeneic pig islets were transplanted into recipient mice in the presence or absence of autoimmunity. Spontaneously, non-...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1034/j.1399-3089.2003.02040.x

    authors: Koulmanda M,Qipo A,Smith RN,Auchincloss H Jr

    更新日期:2003-03-01 00:00:00

  • Toward a solution for cardiac failure in the newborn.

    abstract::The newborn infant with severe cardiac failure owed to congenital structural heart disease or cardiomyopathy poses a daunting therapeutic challenge. The ideal solution for both might be cardiac transplantation if availability of hearts was not limiting and if tolerance could be induced, obviating toxicity of immunosup...

    journal_title:Xenotransplantation

    pub_type: 杂志文章,评审

    doi:10.1111/xen.12479

    authors: Platt JL,West LJ,Chinnock RE,Cascalho M

    更新日期:2018-11-01 00:00:00

  • The effect of soluble complement receptor type 1 on acute humoral xenograft rejection in hDAF-transgenic pig-to-primate life-supporting kidney xenografts.

    abstract:BACKGROUND:In pig-to-nonhuman primate solid organ xenotransplantation using organs from donors transgenic for human decay-accelerating factor (hDAF), the main type of rejection is antibody-mediated (acute humoral xenograft rejection, AHXR). This occurs despite the complement-regulatory function of the transgene, neutra...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/j.1399-3089.2004.00184.x

    authors: Lam TT,Hausen B,Hook L,Lau M,Higgins J,Christians U,Jacobsen W,Baluom M,Duthaler R,Katopodis A,Chavez G,Cozzi E,Harrison R,Schuurman HJ,Borie D,Morris RE

    更新日期:2005-01-01 00:00:00

  • Characterization and quantification of porcine circulating endothelial cells.

    abstract:BACKGROUND:Endothelial damage is a critical step in the development of (xeno) transplantation-related and cardiovascular pathology. In humans, the amount of circulating endothelial cells (CEC) correlates to disease intensity and functions as a valuable damage marker. While (xeno) transplantation and cardiovascular rese...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/xen.12018

    authors: Post IC,Weenink RP,van Wijk AC,Heger M,Böing AN,van Hulst RA,van Gulik TM

    更新日期:2013-01-01 00:00:00

  • Caprine pancreatic islet xenotransplantation into diabetic immunosuppressed BALB/c mice.

    abstract:BACKGROUND:Type 1 diabetes mellitus is a devastating disease for which there is currently no cure, but only lifetime management. Islet xenotransplantation is a promising technique for the restoration of blood glucose control in patients with diabetes mellitus. The purpose of this study was to explore the potential use ...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/xen.12087

    authors: Hani H,Allaudin ZN,Mohd-Lila MA,Ibrahim TA,Othman AM

    更新日期:2014-03-01 00:00:00

  • Systemic inflammation in xenograft recipients precedes activation of coagulation.

    abstract:BACKGROUND:Dysregulation of coagulation is considered a major barrier against successful pig organ xenotransplantation in non-human primates. Inflammation is known to promote activation of coagulation. The role of pro-inflammatory factors as well as the relationship between inflammation and activation of coagulation in...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/xen.12133

    authors: Ezzelarab MB,Ekser B,Azimzadeh A,Lin CC,Zhao Y,Rodriguez R,Echeverri GJ,Iwase H,Long C,Hara H,Ayares D,Pierson RN,Thomson AW,Cooper DK

    更新日期:2015-01-01 00:00:00

  • Chemical cross-linking of xenopericardial biomeshes: A bottom-up study of structural and functional correlations.

    abstract::Decellularized bovine pericardium (DBP)-based biomeshes are the gold standard in reconstructive surgery. In order to prolong their stability after the transplantation, various chemical cross-linking strategies are employed. However, structural and functional properties of the biomeshes differ in dependence on the cros...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/xen.12506

    authors: Grebenik EA,Istranov LP,Istranova EV,Churbanov SN,Shavkuta BS,Dmitriev RI,Veryasova NN,Kotova SL,Kurkov AV,Shekhter AB,Timashev PS

    更新日期:2019-05-01 00:00:00

  • Preconditioning with the prostacyclin analog epoprostenol and cobra venom factor prevents reperfusion injury and hyperacute rejection in discordant liver xenotransplantation.

    abstract::Liver xenografts transplanted from guinea pig to rat suffer from inadequate organ reperfusion and initial dysfunction, despite sufficient complement depletion using cobra venom factor (CVF). Reperfusion injury is prevented when complement depleted donors are treated with the prostacyclin analog epoprostenol. Histologi...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1034/j.1399-3089.2001.00074.x

    authors: Meyer zu Vilsendorf A,Link C,Jörns A,Nagel E,Köhl J

    更新日期:2001-02-01 00:00:00

  • Neonatal porcine pancreatic cell clusters as a potential source for transplantation in humans: characterization of proliferation, apoptosis, xenoantigen expression and gene delivery with recombinant AAV.

    abstract::Neonatal porcine islets are characterized by reproducible isolation success and high yields, sizable advantages over adult islets. In this work we have analyzed selected phenotypic and functional characteristics of porcine neonatal islets relevant to their possible use for transplant in humans. We show that porcine is...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1034/j.1399-3089.2002.0o128.x

    authors: Vizzardelli C,Molano RD,Pileggi A,Berney T,Cattan P,Fenjves ES,Peel A,Fraker C,Ricordi C,Inverardi L

    更新日期:2002-01-01 00:00:00

  • Absence of humoral and cellular alloreactivity in baboons sensitized to pig antigens.

    abstract:AIM:to study whether sensitization to pig antigens results in humoral and/or cellular sensitization to alloantigens in baboons, and thus increases the risks of organ allotransplantation after xenotransplantation. Serum from baboons that were naive (n = 4), sensitized to Gal alpha 1,3Gal (Gal) antigens (n = 2), or sensi...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/j.1399-3089.2004.00075.x

    authors: Baertschiger RM,Dor FJ,Prabharasuth D,Kuwaki K,Cooper DK

    更新日期:2004-01-01 00:00:00

  • History of xenotransplantation.

    abstract::The present historical review reports the clinical experiences of transplantations from animal to human. The first transplantation attempts were made without any knowledge of the species barrier. The pioneers of xenotransplantation realized xenotransfusions as early as the 16th century, then cell and tissue xenotransp...

    journal_title:Xenotransplantation

    pub_type: 历史文章,杂志文章

    doi:10.1111/j.1399-3089.2004.00199.x

    authors: Deschamps JY,Roux FA,Saï P,Gouin E

    更新日期:2005-03-01 00:00:00

  • Characterization of porcine endogenous retrovirus expression in neonatal and adult pig pancreatic islets.

    abstract:BACKGROUND:Pig islets represent an alternative to the current modes of treatment for patients with diabetes. However, the concerns over pathogen transmission including that of PERV limit their immediate, widespread usage in humans. It has been previously demonstrated that PERV copy number and particularly expression le...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/xen.12311

    authors: Mourad NI,Crossan C,Cruikshank V,Scobie L,Gianello P

    更新日期:2017-07-01 00:00:00

  • Pig endogenous retroviruses and xenotransplantation.

    abstract::Xenotransplantation of porcine organs might provide an unlimited source of donor organs to treat endstage organ failure diseases in humans. However, pigs harbour retroviruses with unknown pathogenic potential as an integral part of their genome. While until recently the risk of interspecies transmission of these porci...

    journal_title:Xenotransplantation

    pub_type: 杂志文章,评审

    doi:10.1034/j.1399-3089.2002.01110.x

    authors: Blusch JH,Patience C,Martin U

    更新日期:2002-07-01 00:00:00

  • Encouraging experience using multi-transgenic xenografts in a pig-to-baboon cardiac xenotransplantation model.

    abstract:BACKGROUND:Innovations in transgenic technology have facilitated improved xenograft survival. Additional gene expression appears to be necessary to overcome the remaining immune and biologic incompatibilities. We report for the first time the novel use of six-gene modifications within a pig-to-baboon cardiac xenotransp...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/xen.12330

    authors: Chan JL,Singh AK,Corcoran PC,Thomas ML,Lewis BG,Ayares DL,Vaught T,Horvath KA,Mohiuddin MM

    更新日期:2017-11-01 00:00:00

  • Cyclophosphamide, but not CTLA4Ig, prolongs survival of fetal pig islet grafts in anti-T cell monoclonal antibody-treated NOD mice.

    abstract::Fetal pig islets, xenografted after organ culture into non-immunosuppressed prediabetic NOD mice, are rejected within 10 days. Immunosuppression with anti-T cell (anti-CD4 and anti-CD3) monoclonal antibodies alone is highly effective in delaying graft rejection in this discordant model, but rejection eventually occurs...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/j.1399-3089.1998.tb00030.x

    authors: Koulmanda M,Kovarik J,Mandel TE

    更新日期:1998-08-01 00:00:00

  • Role of P-selectin and P-selectin glycoprotein ligand-1 interaction in the induction of tissue factor expression on human platelets after incubation with porcine aortic endothelial cells.

    abstract::Development of coagulation disorders remains a major challenge in pig-to-primate organ xenotransplantation. Our previous studies demonstrated that porcine aortic endothelial cells (pAEC) activate human platelets to express tissue factor (TF). In this study, we investigated the molecular interaction between human plate...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/xen.12068

    authors: Ezzelarab MB,Liu YW,Lin CC,Long C,Ayares D,Dorling A,Cooper DK

    更新日期:2014-01-01 00:00:00

  • Circulating pig-specific DNA as a novel biomarker for monitoring xenograft rejection.

    abstract::Monitoring for immune rejection is crucial for long-term survival of pig xenografts. Circulating DNA is a promising non-invasive biomarker for either organ injury or response to therapy. In this study, circulating pig-specific DNA (cpsDNA) was monitored during xenograft rejection. Potential targets of cpsDNA were sele...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/xen.12522

    authors: Zhou M,Lu Y,Zhao C,Zhang J,Cooper DKC,Xie C,Song Z,Gao H,Qu Z,Lin S,Deng Y,Hara H,Zhan Y,Jiang Z,Dai Y,Wu C,Cai Z,Mou L

    更新日期:2019-07-01 00:00:00

  • Address by the Honorary Founding President of the Xenotransplantation Society. The eye of an eagle: xenobiology and the quest for bioadvantage.

    abstract::My purpose in these remarks is to stimulate us to consider the vast array that nature has provided us in the differentiation of species, and to examine the possibility that some of these differences might prove useful in other species, including man. ...

    journal_title:Xenotransplantation

    pub_type:

    doi:10.1034/j.1399-3089.2000.00045.x

    authors: Reemtsma K

    更新日期:2000-05-01 00:00:00