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Invited Review: Genetic and Genomic Mouse Models for Livestock Research
Archives Animal Breeding – serving the animal science community for 60 years Arch. Anim. Breed., 61, 87–98, 2018 https://doi.org/10.5194/aab-61-87-2018 Open Access © Author(s) 2018. This work is distributed under the Creative Commons Attribution 4.0 License. Archives Animal Breeding Invited review: Genetic and genomic mouse models for livestock research Danny Arends, Deike Hesse, and Gudrun A. Brockmann Albrecht Daniel Thaer-Institut für Agrar- und Gartenbauwissenschaften, Humboldt-Universität zu Berlin, 10115 Berlin, Germany Correspondence: Danny Arends ([email protected]) and Gudrun A. Brockmann ([email protected]) Received: 7 December 2017 – Revised: 3 January 2018 – Accepted: 8 January 2018 – Published: 13 February 2018 Abstract. Knowledge about the function and functioning of single or multiple interacting genes is of the utmost significance for understanding the organism as a whole and for accurate livestock improvement through genomic selection. This includes, but is not limited to, understanding the ontogenetic and environmentally driven regula- tion of gene action contributing to simple and complex traits. Genetically modified mice, in which the functions of single genes are annotated; mice with reduced genetic complexity; and simplified structured populations are tools to gain fundamental knowledge of inheritance patterns and whole system genetics and genomics. In this re- view, we briefly describe existing mouse resources and discuss their value for fundamental and applied research in livestock. 1 Introduction the generation of targeted mutations found their way from model animals to livestock species. Through this progress, During the last 10 years, tools for genome analyses model organisms attain a new position in fundamental sci- have developed tremendously. -
Inhibition of Hedgehog Signaling Suppresses Proliferation And
www.nature.com/scientificreports OPEN Inhibition of Hedgehog signaling suppresses proliferation and microcyst formation of human Received: 21 August 2017 Accepted: 9 March 2018 Autosomal Dominant Polycystic Published: xx xx xxxx Kidney Disease cells Luciane M. Silva1,5, Damon T. Jacobs1,5, Bailey A. Allard1,5, Timothy A. Fields2,5, Madhulika Sharma4,5, Darren P. Wallace3,4,5 & Pamela V. Tran 1,5 Autosomal Dominant Polycystic Kidney Disease (ADPKD) is caused by mutation of PKD1 or PKD2, which encode polycystin 1 and 2, respectively. The polycystins localize to primary cilia and the functional loss of the polycystin complex leads to the formation and progressive growth of fuid-flled cysts in the kidney. The pathogenesis of ADPKD is complex and molecular mechanisms connecting ciliary dysfunction to renal cystogenesis are unclear. Primary cilia mediate Hedgehog signaling, which modulates cell proliferation and diferentiation in a tissue-dependent manner. Previously, we showed that Hedgehog signaling was increased in cystic kidneys of several PKD mouse models and that Hedgehog inhibition prevented cyst formation in embryonic PKD mouse kidneys treated with cAMP. Here, we show that in human ADPKD tissue, Hedgehog target and activator, Glioma 1, was elevated and localized to cyst-lining epithelial cells and to interstitial cells, suggesting increased autocrine and paracrine Hedgehog signaling in ADPKD, respectively. Further, Hedgehog inhibitors reduced basal and cAMP-induced proliferation of ADPKD cells and cyst formation in vitro. These data suggest that Hedgehog signaling is increased in human ADPKD and that suppression of Hedgehog signaling can counter cellular processes that promote cyst growth in vitro. Autosomal Dominant Polycystic Kidney Disease (ADPKD) is among the most commonly inherited, life-threatening diseases, afecting 1:500 adults worldwide. -
Loss of C. Elegans BBS-7 and BBS-8 Protein Function Results in Cilia Defects and Compromised Intraflagellar Transport
Downloaded from genesdev.cshlp.org on September 29, 2021 - Published by Cold Spring Harbor Laboratory Press Loss of C. elegans BBS-7 and BBS-8 protein function results in cilia defects and compromised intraflagellar transport Oliver E. Blacque,1 Michael J. Reardon,2 Chunmei Li,1 Jonathan McCarthy,1 Moe R. Mahjoub,3 Stephen J. Ansley,4 Jose L. Badano,4 Allan K. Mah,1 Philip L. Beales,6 William S. Davidson,1 Robert C. Johnsen,1 Mark Audeh,2 Ronald H.A. Plasterk,7 David L. Baillie,1 Nicholas Katsanis,4,5 Lynne M. Quarmby,3 Stephen R. Wicks,2 and Michel R. Leroux1,8 1Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, B.C. V5A 1S6, Canada; 2Department of Biology, Boston College, Chestnut Hill, Massachusetts 02467, USA; 3Department of Biological Sciences, Simon Fraser University, Burnaby, B.C. V5A 1S6, Canada; 4Institute of Genetic Medicine and 5Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland 21287, USA; 6Molecular Medicine Unit, Institute of Child Health, University College London, London WC1 1EH, UK; 7The Hubrecht Laboratory, Netherlands Institute of Developmental Biology, Uppsalalaan 8, 3584CT, Utrecht, The Netherlands Bardet-Biedl syndrome (BBS) is a genetically heterogeneous developmental disorder whose molecular basis is largely unknown. Here, we show that mutations in the Caenorhabditis elegans bbs-7 and bbs-8 genes cause structural and functional defects in cilia. C. elegans BBS proteins localize predominantly at the base of cilia, and like proteins involved in intraflagellar transport (IFT), a process necessary for cilia biogenesis and maintenance, move bidirectionally along the ciliary axoneme. Importantly, we demonstrate that BBS-7 and BBS-8 are required for the normal localization/motility of the IFT proteins OSM-5/Polaris and CHE-11, and to a notably lesser extent, CHE-2. -
Knockdown of the BBS10 Gene Product
ndrom Sy es tic & e G n e e n G e f T o Zacchia et al., J Genet Syndr Gene Ther 2014, 5:3 Journal of Genetic Syndromes h l e a r n a DOI: 10.4172/2157-7412.1000222 r p u y o J ISSN: 2157-7412 & Gene Therapy Research Article Open Access Knockdown of the BBS10 Gene Product Affects Apical Targeting of AQP2 in Renal Cells: A Possible Explanation for the Polyuria Associated with Bardet-Biedl Syndrome Miriam Zacchia1, Gabriella Esposito2,3, Monica Carmosino7, Claudia Barbieri7, Enza Zacchia1,5, Alessia Anna Crispo2, Tiziana Fioretti2,3, Francesco Trepiccione1, Valentina Di Iorio6, Francesca Simonelli6, Francesco Salvatore2,4, Giovambattista Capasso1, Maria Svelto7,8 and Giuseppe Procino7,8* 1Chair of Nephrology, Second University of Naples, Italy 2CEINGE-Biotecnologie Avanzate s.c. a r.l., Naples, Italy 3Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Italy 4IRCCS SDN Foundation Naples, Italy 5Institute of Genetics and Biophysics of the National Research Council (CNR), Naples, Italy 6Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences - Second University of Naples, Italy 7Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Italy 8Center of Excellence in Comparative Genomics, Bari, Italy Abstract Objective: Bardet-Biedl syndrome (BBS) is a rare genetic disorder whose clinical features include renal abnormalities, which ranges from renal malformations to renal failure. Polyuria and iso-hyposthenuria are common renal dysfunctions in BBS patients even in the presence of normal GFR. The mechanism underlying this defect is unknown and no genotype-phenotype correlation has yet been reported. -
Transmission Distortion and Genetic Incompatibilities Between Alleles in A
bioRxiv preprint doi: https://doi.org/10.1101/2021.06.09.447720; this version posted June 10, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Transmission distortion and genetic incompatibilities between alleles in a 2 multigenerational mouse advanced intercross line 3 Danny Arends, [email protected], Albrecht Daniel Thaer-Institut für Agrar- und 4 Gartenbauwissenschaften, Humboldt-Universität zu Berlin, Invalidenstraße 42, D-10115 Berlin, 5 Germany 6 Stefan Kärst, [email protected], Albrecht Daniel Thaer-Institut für Agrar- und 7 Gartenbauwissenschaften, Humboldt-Universität zu Berlin, Invalidenstraße 42, D-10115 Berlin, 8 Germany 9 Sebastian Heise, [email protected], Albrecht Daniel Thaer-Institut für Agrar- und 10 Gartenbauwissenschaften, Humboldt-Universität zu Berlin, Invalidenstraße 42, D-10115 Berlin, 11 Germany 12 Paula Korkuc, [email protected], Albrecht Daniel Thaer-Institut für Agrar- und 13 Gartenbauwissenschaften, Humboldt-Universität zu Berlin, Invalidenstraße 42, D-10115 Berlin, 14 Germany 15 Deike Hesse, [email protected], Albrecht Daniel Thaer-Institut für Agrar- und 16 Gartenbauwissenschaften, Humboldt-Universität zu Berlin, Invalidenstraße 42, D-10115 Berlin, 17 Germany 18 Gudrun A. Brockmann†, [email protected], Albrecht Daniel Thaer-Institut für Agrar- 19 und Gartenbauwissenschaften, Humboldt-Universität zu Berlin, Invalidenstraße 42, D-10115 Berlin, 20 Germany 21 † To whom correspondence should be addressed. 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.06.09.447720; this version posted June 10, 2021. -
Mouse Mutants As Models for Congenital Retinal Disorders
Experimental Eye Research 81 (2005) 503–512 www.elsevier.com/locate/yexer Review Mouse mutants as models for congenital retinal disorders Claudia Dalke*, Jochen Graw GSF-National Research Center for Environment and Health, Institute of Developmental Genetics, D-85764 Neuherberg, Germany Received 1 February 2005; accepted in revised form 1 June 2005 Available online 18 July 2005 Abstract Animal models provide a valuable tool for investigating the genetic basis and the pathophysiology of human diseases, and to evaluate therapeutic treatments. To study congenital retinal disorders, mouse mutants have become the most important model organism. Here we review some mouse models, which are related to hereditary disorders (mostly congenital) including retinitis pigmentosa, Leber’s congenital amaurosis, macular disorders and optic atrophy. q 2005 Elsevier Ltd. All rights reserved. Keywords: animal model; retina; mouse; gene mutation; retinal degeneration 1. Introduction Although mouse models are a good tool to investigate retinal disorders, one should keep in mind that the mouse Mice suffering from hereditary eye defects (and in retina is somehow different from a human retina, particular from retinal degenerations) have been collected particularly with respect to the number and distribution of since decades (Keeler, 1924). They allow the study of the photoreceptor cells. The mouse as a nocturnal animal molecular and histological development of retinal degener- has a retina dominated by rods; in contrast, cones are small ations and to characterize the genetic basis underlying in size and represent only 3–5% of the photoreceptors. Mice retinal dysfunction and degeneration. The recent progress of do not form cone-rich areas like the human fovea. -
Composition and Function of the C1b/C1f Region in the Ciliary Central
www.nature.com/scientificreports OPEN Composition and function of the C1b/C1f region in the ciliary central apparatus Ewa Joachimiak 1*, Anna Osinka 1, Hanan Farahat 1, Bianka Świderska 2, Ewa Sitkiewicz 2, Martyna Poprzeczko 1,3, Hanna Fabczak 1 & Dorota Wloga 1* Motile cilia are ultrastructurally complex cell organelles with the ability to actively move. The highly conserved central apparatus of motile 9 × 2 + 2 cilia is composed of two microtubules and several large microtubule-bound projections, including the C1b/C1f supercomplex. The composition and function of C1b/C1f subunits has only recently started to emerge. We show that in the model ciliate Tetrahymena thermophila, C1b/C1f contains several evolutionarily conserved proteins: Spef2A, Cfap69, Cfap246/ LRGUK, Adgb/androglobin, and a ciliate-specifc protein Tt170/TTHERM_00205170. Deletion of genes encoding either Spef2A or Cfap69 led to a loss of the entire C1b projection and resulted in an abnormal vortex motion of cilia. Loss of either Cfap246 or Adgb caused only minor alterations in ciliary motility. Comparative analyses of wild-type and C1b-defcient mutant ciliomes revealed that the levels of subunits forming the adjacent C2b projection but not C1d projection are greatly reduced, indicating that C1b stabilizes C2b. Moreover, the levels of several IFT and BBS proteins, HSP70, and enzymes that catalyze the fnal steps of the glycolytic pathway: enolase ENO1 and pyruvate kinase PYK1, are also reduced in the C1b-less mutants. Motile cilia and structurally homologous eukaryotic fagella are complex biological nanomachines that propagate fuids and particles along the surface of ciliated epithelia, and power cell motility of protists, zoospores, and male gametes. -
BBS7 Is Required for Bbsome Formation and Its Absence in Mice
2372 Research Article BBS7 is required for BBSome formation and its absence in mice results in Bardet-Biedl syndrome phenotypes and selective abnormalities in membrane protein trafficking Qihong Zhang1, Darryl Nishimura1, Tim Vogel2, Jianqiang Shao3, Ruth Swiderski1, Terry Yin4, Charles Searby1, Calvin S. Carter5, GunHee Kim1, Kevin Bugge1, Edwin M. Stone6 and Val C. Sheffield1,* 1Department of Pediatrics, Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242, USA 2Department of Neurosurgery, University of Iowa, Iowa City, IA 52242, USA 3Central Microscopy Research Facilities, University of Iowa, Iowa City, IA 52242, USA 4Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA 5Program in Neuroscience, University of Iowa, Iowa City, IA 52242, USA 6Department of Ophthalmology and Visual Sciences, Howard Hughes Medical Institute, University of Iowa, Iowa City 52242, USA *Author for correspondence ([email protected]) Accepted 18 March 2013 Journal of Cell Science 126, 2372–2380 ß 2013. Published by The Company of Biologists Ltd doi: 10.1242/jcs.111740 Summary Bardet-Biedl Syndrome (BBS) is a pleiotropic and genetically heterozygous disorder caused independently by numerous genes (BBS1– BBS17). Seven highly conserved BBS proteins (BBS1, 2, 4, 5, 7, 8 and 9) form a complex known as the BBSome, which functions in ciliary membrane biogenesis. BBS7 is both a unique subunit of the BBSome and displays direct physical interaction with a second BBS complex, the BBS chaperonin complex. To examine the in vivo function of BBS7, we generated Bbs7 knockout mice. Bbs72/2 mice show similar phenotypes to other BBS gene mutant mice including retinal degeneration, obesity, ventriculomegaly and male infertility characterized by abnormal spermatozoa flagellar axonemes. -
BBS6, BBS10, and BBS12 Form a Complex with CCT/Tric Family Chaperonins and Mediate Bbsome Assembly
BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly Seongjin Seoa,c, Lisa M. Bayeb, Nathan P. Schulza,c, John S. Becka,c, Qihong Zhanga,c, Diane C. Slusarskib, and Val C. Sheffielda,c,1 aDepartment of Pediatrics, bDepartment of Biology, and cHoward Hughes Medical Institute, University of Iowa, Iowa City, IA 52242 Edited by Kathryn V. Anderson, Sloan-Kettering Institute, New York, NY, and approved November 25, 2009 (received for review September 9, 2009) Bardet-Biedl syndrome (BBS) is a human genetic disorder resulting one component of the BBSome, BBS1, directly interacts with the in obesity, retinal degeneration, polydactyly, and nephropathy. leptin receptor and that leptin signaling is attenuated in BBS Recent studies indicate that trafficking defects to the ciliary mem- gene knockout mice, implicating BBS function in a broad range brane are involved in this syndrome. Here, we show that a novel of membrane receptor signaling (33). complex composed of three chaperonin-like BBS proteins (BBS6, Three of the remaining BBS proteins (BBS6, BBS10, and BBS10, and BBS12) and CCT/TRiC family chaperonins mediates BBS12) have sequence homology to the CCT (also known as BBSome assembly, which transports vesicles to the cilia. Chaperonin- TRiC) family of group II chaperonins (17, 24, 25). CCT proteins like BBS proteins interact with a subset of BBSome subunits and form an ≈900 kDa hetero-oligomeric complex that mediates promote their association with CCT chaperonins. CCT activity is protein folding in an ATP-dependent manner (34, 35). The CCT essential for BBSome assembly, and knockdown of CCT chaperonins complex consists of two stacked rings, each of which is composed in zebrafish results in BBS phenotypes. -
UC San Francisco Previously Published Works
UCSF UC San Francisco Previously Published Works Title FitSNPs: highly differentially expressed genes are more likely to have variants associated with disease. Permalink https://escholarship.org/uc/item/91k8p2km Journal Genome biology, 9(12) ISSN 1474-7596 Authors Chen, Rong Morgan, Alex A Dudley, Joel et al. Publication Date 2008 DOI 10.1186/gb-2008-9-12-r170 Peer reviewed eScholarship.org Powered by the California Digital Library University of California Open Access Research2008ChenetVolume al. 9, Issue 12, Article R170 FitSNPs: highly differentially expressed genes are more likely to have variants associated with disease Rong Chen*†‡, Alex A Morgan*†‡, Joel Dudley*†‡, Tarangini Deshpande§, Li Li†, Keiichi Kodama*†‡, Annie P Chiang*†‡ and Atul J Butte*†‡ Addresses: *Stanford Center for Biomedical Informatics Research, 251 Cmpus Drive, Stanford, CA 94305, USA. †Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA. ‡Lucile Packard Children's Hospital, 725 Welch Road, Palo Alto, CA 94304, USA. §NuMedii Inc., Menlo Park, CA 94025, USA. Correspondence: Atul J Butte. Email: [email protected] Published: 5 December 2008 Received: 17 June 2008 Revised: 26 September 2008 Genome Biology 2008, 9:R170 (doi:10.1186/gb-2008-9-12-r170) Accepted: 5 December 2008 The electronic version of this article is the complete one and can be found online at http://genomebiology.com/2008/9/12/R170 © 2008 Chen et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. -
Microrna-124-3P Suppresses Mouse Lip Mesenchymal Cell Proliferation
Suzuki et al. BMC Genomics (2019) 20:852 https://doi.org/10.1186/s12864-019-6238-4 RESEARCH ARTICLE Open Access MicroRNA-124-3p suppresses mouse lip mesenchymal cell proliferation through the regulation of genes associated with cleft lip in the mouse Akiko Suzuki1,2, Hiroki Yoshioka1,2, Dima Summakia1, Neha G. Desai1,3, Goo Jun3,4, Peilin Jia5, David S. Loose4,6, Kenichi Ogata1,2, Mona V. Gajera1,3, Zhongming Zhao3,4,5 and Junichi Iwata1,2,4* Abstract Background: Cleft lip (CL), one of the most common congenital birth defects, shows considerable geographic and ethnic variation, with contribution of both genetic and environmental factors. Mouse genetic studies have identified several CL-associated genes. However, it remains elusive how these CL-associated genes are regulated and involved in CL. Environmental factors may regulate these genes at the post-transcriptional level through the regulation of non-coding microRNAs (miRNAs). In this study, we sought to identify miRNAs associated with CL in mice. Results: Through a systematic literature review and a Mouse Genome Informatics (MGI) database search, we identified 55 genes that were associated with CL in mice. Subsequent bioinformatic analysis of these genes predicted that a total of 33 miRNAs target multiple CL-associated genes, with 20 CL-associated genes being potentially regulated by multiple miRNAs. To experimentally validate miRNA function in cell proliferation, we conducted cell proliferation/viability assays for the selected five candidate miRNAs (miR-124-3p, let-7a-5p, let-7b-5p, let-7c-5p, and let-7d-5p). Overexpression of miR-124-3p, but not of the others, inhibited cell proliferation through suppression of CL-associated genes in cultured mouse embryonic lip mesenchymal cells (MELM cells) isolated from the developing mouse lip region. -
Supplementary Information – Postema Et Al., the Genetics of Situs Inversus Totalis Without Primary Ciliary Dyskinesia
1 Supplementary information – Postema et al., The genetics of situs inversus totalis without primary ciliary dyskinesia Table of Contents: Supplementary Methods 2 Supplementary Results 5 Supplementary References 6 Supplementary Tables and Figures Table S1. Subject characteristics 9 Table S2. Inbreeding coefficients per subject 10 Figure S1. Multidimensional scaling to capture overall genomic diversity 11 among the 30 study samples Table S3. Significantly enriched gene-sets under a recessive mutation model 12 Table S4. Broader list of candidate genes, and the sources that led to their 13 inclusion Table S5. Potential recessive and X-linked mutations in the unsolved cases 15 Table S6. Potential mutations in the unsolved cases, dominant model 22 2 1.0 Supplementary Methods 1.1 Participants Fifteen people with radiologically documented SIT, including nine without PCD and six with Kartagener syndrome, and 15 healthy controls matched for age, sex, education and handedness, were recruited from Ghent University Hospital and Middelheim Hospital Antwerp. Details about the recruitment and selection procedure have been described elsewhere (1). Briefly, among the 15 people with radiologically documented SIT, those who had symptoms reminiscent of PCD, or who were formally diagnosed with PCD according to their medical record, were categorized as having Kartagener syndrome. Those who had no reported symptoms or formal diagnosis of PCD were assigned to the non-PCD SIT group. Handedness was assessed using the Edinburgh Handedness Inventory (EHI) (2). Tables 1 and S1 give overviews of the participants and their characteristics. Note that one non-PCD SIT subject reported being forced to switch from left- to right-handedness in childhood, in which case five out of nine of the non-PCD SIT cases are naturally left-handed (Table 1, Table S1).