The Chihuahua dog: A new animal model for neuronal ceroid lipofuscinosis CLN7 disease?

Neuronal ceroid lipofuscinoses (NCLs) are a group of incurable lysosomal storage disorders characterized by neurodegeneration and accumulation of lipopigments mainly within the neurons. We studied two littermate Chihuahua dogs presenting with progressive signs of blindness, ataxia, pacing, and cogni...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Journal of neuroscience research 2016-04, Vol.94 (4), p.339-347
Hauptverfasser: Faller, Kiterie M.E., Bras, Jose, Sharpe, Samuel J., Anderson, Glenn W., Darwent, Lee, Kun-Rodrigues, Celia, Alroy, Joseph, Penderis, Jacques, Mole, Sara E., Gutierrez-Quintana, Rodrigo, Guerreiro, Rita J.
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 347
container_issue 4
container_start_page 339
container_title Journal of neuroscience research
container_volume 94
creator Faller, Kiterie M.E.
Bras, Jose
Sharpe, Samuel J.
Anderson, Glenn W.
Darwent, Lee
Kun-Rodrigues, Celia
Alroy, Joseph
Penderis, Jacques
Mole, Sara E.
Gutierrez-Quintana, Rodrigo
Guerreiro, Rita J.
description Neuronal ceroid lipofuscinoses (NCLs) are a group of incurable lysosomal storage disorders characterized by neurodegeneration and accumulation of lipopigments mainly within the neurons. We studied two littermate Chihuahua dogs presenting with progressive signs of blindness, ataxia, pacing, and cognitive impairment from 1 year of age. Because of worsening of clinical signs, both dogs were euthanized at about 2 years of age. Postmortem examination revealed marked accumulation of autofluorescent intracellular inclusions within the brain, characteristic of NCL. Whole‐genome sequencing was performed on one of the affected dogs. After sequence alignment and variant calling against the canine reference genome, variants were identified in the coding region or splicing regions of four previously known NCL genes (CLN6, ARSG, CLN2 [=TPP1], and CLN7 [=MFSD8]). Subsequent segregation analysis within the family (two affected dogs, both parents, and three relatives) identified MFSD8:p.Phe282Leufs13*, which had previously been identified in one Chinese crested dog with no available ancestries, as the causal mutation. Because of the similarities of the clinical signs and histopathological changes with the human form of the disease, we propose that the Chihuahua dog could be a good animal model of CLN7 disease. © 2016 Wiley Periodicals, Inc. A single pair deletion in MFSD8 (=CLN7) results in neuronal ceroid lipofuscinosis in Chihuahua dogs. These dogs represent an excellent animal model opportunity for this poorly understood NCL form because they closely mimic the human phenotype of the disease.
doi_str_mv 10.1002/jnr.23710
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1780518057</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1780518057</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5950-2d4055e90ef797cc84121edc633c722735bcdf0734a4089241e8687caed5e6b63</originalsourceid><addsrcrecordid>eNqN0U9rFDEYBvAgit1WD34BCXjRw7Rv_k-8lLLYal1W0No9htnMO27W2cmadGj77U3dtgdBEBICL788kDyEvGJwyAD40XpIh1wYBk_IhIE1lVTSPCUTEBoqCYzvkf2c1wBgrRLPyR7XRnNm5IRcXqyQTldhNTZl0Tb-eE9P6IDXtBnCpunpJrbY0y6mMhxTHMrIY4qhpX3Yxm7MPgwxh0yns7mhbcjYZDx-QZ51TZ_x5f15QL6ffriYfqxmX84-TU9mlVdWQcVbCUqhBeyMNd7XknGGrddCeMO5EWrp2w6MkI2E2nLJsNa18Q22CvVSiwPydpe7TfHXiPnKbUL22PfNgHHMjpkaFCvb_AfV3Cpra1nom7_oOo6pPH2njLSM3al3O-VTzDlh57apfFm6dQzcXS-u9OL-9FLs6_vEcbnB9lE-FFHA0Q5chx5v_53kzudfHyKr3Y2Qr_Dm8UaTfjpthFFuMT9z3xbnnxeXoN2p-A275aNh</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1762749114</pqid></control><display><type>article</type><title>The Chihuahua dog: A new animal model for neuronal ceroid lipofuscinosis CLN7 disease?</title><source>MEDLINE</source><source>Wiley Journals</source><creator>Faller, Kiterie M.E. ; Bras, Jose ; Sharpe, Samuel J. ; Anderson, Glenn W. ; Darwent, Lee ; Kun-Rodrigues, Celia ; Alroy, Joseph ; Penderis, Jacques ; Mole, Sara E. ; Gutierrez-Quintana, Rodrigo ; Guerreiro, Rita J.</creator><creatorcontrib>Faller, Kiterie M.E. ; Bras, Jose ; Sharpe, Samuel J. ; Anderson, Glenn W. ; Darwent, Lee ; Kun-Rodrigues, Celia ; Alroy, Joseph ; Penderis, Jacques ; Mole, Sara E. ; Gutierrez-Quintana, Rodrigo ; Guerreiro, Rita J.</creatorcontrib><description>Neuronal ceroid lipofuscinoses (NCLs) are a group of incurable lysosomal storage disorders characterized by neurodegeneration and accumulation of lipopigments mainly within the neurons. We studied two littermate Chihuahua dogs presenting with progressive signs of blindness, ataxia, pacing, and cognitive impairment from 1 year of age. Because of worsening of clinical signs, both dogs were euthanized at about 2 years of age. Postmortem examination revealed marked accumulation of autofluorescent intracellular inclusions within the brain, characteristic of NCL. Whole‐genome sequencing was performed on one of the affected dogs. After sequence alignment and variant calling against the canine reference genome, variants were identified in the coding region or splicing regions of four previously known NCL genes (CLN6, ARSG, CLN2 [=TPP1], and CLN7 [=MFSD8]). Subsequent segregation analysis within the family (two affected dogs, both parents, and three relatives) identified MFSD8:p.Phe282Leufs13*, which had previously been identified in one Chinese crested dog with no available ancestries, as the causal mutation. Because of the similarities of the clinical signs and histopathological changes with the human form of the disease, we propose that the Chihuahua dog could be a good animal model of CLN7 disease. © 2016 Wiley Periodicals, Inc. A single pair deletion in MFSD8 (=CLN7) results in neuronal ceroid lipofuscinosis in Chihuahua dogs. These dogs represent an excellent animal model opportunity for this poorly understood NCL form because they closely mimic the human phenotype of the disease.</description><identifier>ISSN: 0360-4012</identifier><identifier>EISSN: 1097-4547</identifier><identifier>DOI: 10.1002/jnr.23710</identifier><identifier>PMID: 26762174</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Animals ; Disease Models, Animal ; Dogs ; Female ; lysosomal storage disorder ; Male ; Membrane Transport Proteins - genetics ; MFSD8 ; neurodegeneration ; Neuronal Ceroid-Lipofuscinoses - genetics ; Neuronal Ceroid-Lipofuscinoses - pathology ; Neuronal Ceroid-Lipofuscinoses - veterinary ; Polymerase Chain Reaction</subject><ispartof>Journal of neuroscience research, 2016-04, Vol.94 (4), p.339-347</ispartof><rights>2016 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5950-2d4055e90ef797cc84121edc633c722735bcdf0734a4089241e8687caed5e6b63</citedby><cites>FETCH-LOGICAL-c5950-2d4055e90ef797cc84121edc633c722735bcdf0734a4089241e8687caed5e6b63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjnr.23710$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjnr.23710$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26762174$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Faller, Kiterie M.E.</creatorcontrib><creatorcontrib>Bras, Jose</creatorcontrib><creatorcontrib>Sharpe, Samuel J.</creatorcontrib><creatorcontrib>Anderson, Glenn W.</creatorcontrib><creatorcontrib>Darwent, Lee</creatorcontrib><creatorcontrib>Kun-Rodrigues, Celia</creatorcontrib><creatorcontrib>Alroy, Joseph</creatorcontrib><creatorcontrib>Penderis, Jacques</creatorcontrib><creatorcontrib>Mole, Sara E.</creatorcontrib><creatorcontrib>Gutierrez-Quintana, Rodrigo</creatorcontrib><creatorcontrib>Guerreiro, Rita J.</creatorcontrib><title>The Chihuahua dog: A new animal model for neuronal ceroid lipofuscinosis CLN7 disease?</title><title>Journal of neuroscience research</title><addtitle>Journal of Neuroscience Research</addtitle><description>Neuronal ceroid lipofuscinoses (NCLs) are a group of incurable lysosomal storage disorders characterized by neurodegeneration and accumulation of lipopigments mainly within the neurons. We studied two littermate Chihuahua dogs presenting with progressive signs of blindness, ataxia, pacing, and cognitive impairment from 1 year of age. Because of worsening of clinical signs, both dogs were euthanized at about 2 years of age. Postmortem examination revealed marked accumulation of autofluorescent intracellular inclusions within the brain, characteristic of NCL. Whole‐genome sequencing was performed on one of the affected dogs. After sequence alignment and variant calling against the canine reference genome, variants were identified in the coding region or splicing regions of four previously known NCL genes (CLN6, ARSG, CLN2 [=TPP1], and CLN7 [=MFSD8]). Subsequent segregation analysis within the family (two affected dogs, both parents, and three relatives) identified MFSD8:p.Phe282Leufs13*, which had previously been identified in one Chinese crested dog with no available ancestries, as the causal mutation. Because of the similarities of the clinical signs and histopathological changes with the human form of the disease, we propose that the Chihuahua dog could be a good animal model of CLN7 disease. © 2016 Wiley Periodicals, Inc. A single pair deletion in MFSD8 (=CLN7) results in neuronal ceroid lipofuscinosis in Chihuahua dogs. These dogs represent an excellent animal model opportunity for this poorly understood NCL form because they closely mimic the human phenotype of the disease.</description><subject>Animals</subject><subject>Disease Models, Animal</subject><subject>Dogs</subject><subject>Female</subject><subject>lysosomal storage disorder</subject><subject>Male</subject><subject>Membrane Transport Proteins - genetics</subject><subject>MFSD8</subject><subject>neurodegeneration</subject><subject>Neuronal Ceroid-Lipofuscinoses - genetics</subject><subject>Neuronal Ceroid-Lipofuscinoses - pathology</subject><subject>Neuronal Ceroid-Lipofuscinoses - veterinary</subject><subject>Polymerase Chain Reaction</subject><issn>0360-4012</issn><issn>1097-4547</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqN0U9rFDEYBvAgit1WD34BCXjRw7Rv_k-8lLLYal1W0No9htnMO27W2cmadGj77U3dtgdBEBICL788kDyEvGJwyAD40XpIh1wYBk_IhIE1lVTSPCUTEBoqCYzvkf2c1wBgrRLPyR7XRnNm5IRcXqyQTldhNTZl0Tb-eE9P6IDXtBnCpunpJrbY0y6mMhxTHMrIY4qhpX3Yxm7MPgwxh0yns7mhbcjYZDx-QZ51TZ_x5f15QL6ffriYfqxmX84-TU9mlVdWQcVbCUqhBeyMNd7XknGGrddCeMO5EWrp2w6MkI2E2nLJsNa18Q22CvVSiwPydpe7TfHXiPnKbUL22PfNgHHMjpkaFCvb_AfV3Cpra1nom7_oOo6pPH2njLSM3al3O-VTzDlh57apfFm6dQzcXS-u9OL-9FLs6_vEcbnB9lE-FFHA0Q5chx5v_53kzudfHyKr3Y2Qr_Dm8UaTfjpthFFuMT9z3xbnnxeXoN2p-A275aNh</recordid><startdate>201604</startdate><enddate>201604</enddate><creator>Faller, Kiterie M.E.</creator><creator>Bras, Jose</creator><creator>Sharpe, Samuel J.</creator><creator>Anderson, Glenn W.</creator><creator>Darwent, Lee</creator><creator>Kun-Rodrigues, Celia</creator><creator>Alroy, Joseph</creator><creator>Penderis, Jacques</creator><creator>Mole, Sara E.</creator><creator>Gutierrez-Quintana, Rodrigo</creator><creator>Guerreiro, Rita J.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>201604</creationdate><title>The Chihuahua dog: A new animal model for neuronal ceroid lipofuscinosis CLN7 disease?</title><author>Faller, Kiterie M.E. ; Bras, Jose ; Sharpe, Samuel J. ; Anderson, Glenn W. ; Darwent, Lee ; Kun-Rodrigues, Celia ; Alroy, Joseph ; Penderis, Jacques ; Mole, Sara E. ; Gutierrez-Quintana, Rodrigo ; Guerreiro, Rita J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5950-2d4055e90ef797cc84121edc633c722735bcdf0734a4089241e8687caed5e6b63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Disease Models, Animal</topic><topic>Dogs</topic><topic>Female</topic><topic>lysosomal storage disorder</topic><topic>Male</topic><topic>Membrane Transport Proteins - genetics</topic><topic>MFSD8</topic><topic>neurodegeneration</topic><topic>Neuronal Ceroid-Lipofuscinoses - genetics</topic><topic>Neuronal Ceroid-Lipofuscinoses - pathology</topic><topic>Neuronal Ceroid-Lipofuscinoses - veterinary</topic><topic>Polymerase Chain Reaction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Faller, Kiterie M.E.</creatorcontrib><creatorcontrib>Bras, Jose</creatorcontrib><creatorcontrib>Sharpe, Samuel J.</creatorcontrib><creatorcontrib>Anderson, Glenn W.</creatorcontrib><creatorcontrib>Darwent, Lee</creatorcontrib><creatorcontrib>Kun-Rodrigues, Celia</creatorcontrib><creatorcontrib>Alroy, Joseph</creatorcontrib><creatorcontrib>Penderis, Jacques</creatorcontrib><creatorcontrib>Mole, Sara E.</creatorcontrib><creatorcontrib>Gutierrez-Quintana, Rodrigo</creatorcontrib><creatorcontrib>Guerreiro, Rita J.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of neuroscience research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Faller, Kiterie M.E.</au><au>Bras, Jose</au><au>Sharpe, Samuel J.</au><au>Anderson, Glenn W.</au><au>Darwent, Lee</au><au>Kun-Rodrigues, Celia</au><au>Alroy, Joseph</au><au>Penderis, Jacques</au><au>Mole, Sara E.</au><au>Gutierrez-Quintana, Rodrigo</au><au>Guerreiro, Rita J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Chihuahua dog: A new animal model for neuronal ceroid lipofuscinosis CLN7 disease?</atitle><jtitle>Journal of neuroscience research</jtitle><addtitle>Journal of Neuroscience Research</addtitle><date>2016-04</date><risdate>2016</risdate><volume>94</volume><issue>4</issue><spage>339</spage><epage>347</epage><pages>339-347</pages><issn>0360-4012</issn><eissn>1097-4547</eissn><abstract>Neuronal ceroid lipofuscinoses (NCLs) are a group of incurable lysosomal storage disorders characterized by neurodegeneration and accumulation of lipopigments mainly within the neurons. We studied two littermate Chihuahua dogs presenting with progressive signs of blindness, ataxia, pacing, and cognitive impairment from 1 year of age. Because of worsening of clinical signs, both dogs were euthanized at about 2 years of age. Postmortem examination revealed marked accumulation of autofluorescent intracellular inclusions within the brain, characteristic of NCL. Whole‐genome sequencing was performed on one of the affected dogs. After sequence alignment and variant calling against the canine reference genome, variants were identified in the coding region or splicing regions of four previously known NCL genes (CLN6, ARSG, CLN2 [=TPP1], and CLN7 [=MFSD8]). Subsequent segregation analysis within the family (two affected dogs, both parents, and three relatives) identified MFSD8:p.Phe282Leufs13*, which had previously been identified in one Chinese crested dog with no available ancestries, as the causal mutation. Because of the similarities of the clinical signs and histopathological changes with the human form of the disease, we propose that the Chihuahua dog could be a good animal model of CLN7 disease. © 2016 Wiley Periodicals, Inc. A single pair deletion in MFSD8 (=CLN7) results in neuronal ceroid lipofuscinosis in Chihuahua dogs. These dogs represent an excellent animal model opportunity for this poorly understood NCL form because they closely mimic the human phenotype of the disease.</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>26762174</pmid><doi>10.1002/jnr.23710</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0360-4012
ispartof Journal of neuroscience research, 2016-04, Vol.94 (4), p.339-347
issn 0360-4012
1097-4547
language eng
recordid cdi_proquest_miscellaneous_1780518057
source MEDLINE; Wiley Journals
subjects Animals
Disease Models, Animal
Dogs
Female
lysosomal storage disorder
Male
Membrane Transport Proteins - genetics
MFSD8
neurodegeneration
Neuronal Ceroid-Lipofuscinoses - genetics
Neuronal Ceroid-Lipofuscinoses - pathology
Neuronal Ceroid-Lipofuscinoses - veterinary
Polymerase Chain Reaction
title The Chihuahua dog: A new animal model for neuronal ceroid lipofuscinosis CLN7 disease?
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T23%3A25%3A31IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20Chihuahua%20dog:%20A%20new%20animal%20model%20for%20neuronal%20ceroid%20lipofuscinosis%20CLN7%20disease?&rft.jtitle=Journal%20of%20neuroscience%20research&rft.au=Faller,%20Kiterie%20M.E.&rft.date=2016-04&rft.volume=94&rft.issue=4&rft.spage=339&rft.epage=347&rft.pages=339-347&rft.issn=0360-4012&rft.eissn=1097-4547&rft_id=info:doi/10.1002/jnr.23710&rft_dat=%3Cproquest_cross%3E1780518057%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1762749114&rft_id=info:pmid/26762174&rfr_iscdi=true