Genetic Modification of Hearing in Tubby Mice: Evidence for the Existence of a Major Gene (moth1) Which Protects Tubby Mice from Hearing Loss
Quantitative trait locus (QTL) analysis of genetic crosses has proven to be a useful tool for identifying loci associated with specific phenotypes and for dissecting genetic components of complex traits.Inclusion of a mutation that interacts epistatically with QTLs in genetic crosses is a unique and...
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| Veröffentlicht in: | Human molecular genetics 1999-09, Vol.8 (9), p.1761-1767 |
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| creator | Ikeda, Akihiro Yin Zheng, Qing Rosenstiel, Philip Maddatu, Terry Zuberi, Aamir R. Roopenian, Derry C. North, Michael A. Naggert, Jürgen K. Johnson, Kenneth R. Nishina, Patsy M. |
| description | Quantitative trait locus (QTL) analysis of genetic crosses has proven to be a useful tool for identifying loci associated with specific phenotypes and for dissecting genetic components of complex traits.Inclusion of a mutation that interacts epistatically with QTLs in genetic crosses is a unique and potentially powerful method of revealing the function of novel genes and pathways. Although we know that a mutation within the novel tubgene leads to obesity and cochlear and retinal degeneration, the biological function of the gene and the mechanism by which it induces its phenotypes are not known. In the current study, a QTL analysis for auditory brainstem response (ABR) thresholds, which indicates hearing ability, was performed in tubby mice from F2 intercrosses between C57BL/6J-tub/tub and AKR/J−+/+ F1 hybrids (AKR intercross) and between C57BL/6J-tub/ tub and CAST/Ei.B6-tub/tub F1 hybrids (CAST intercross). A major QTL, designated as modifier of tubby hearingl (mothl,) was identified on chromosome 2 with aLOD scoreof 33.4(P |
| doi_str_mv | 10.1093/hmg/8.9.1761 |
| format | Article |
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Although we know that a mutation within the novel tubgene leads to obesity and cochlear and retinal degeneration, the biological function of the gene and the mechanism by which it induces its phenotypes are not known. In the current study, a QTL analysis for auditory brainstem response (ABR) thresholds, which indicates hearing ability, was performed in tubby mice from F2 intercrosses between C57BL/6J-tub/tub and AKR/J−+/+ F1 hybrids (AKR intercross) and between C57BL/6J-tub/ tub and CAST/Ei.B6-tub/tub F1 hybrids (CAST intercross). A major QTL, designated as modifier of tubby hearingl (mothl,) was identified on chromosome 2 with aLOD scoreof 33.4(P<10−33) in the AKR intercross (181 mice) and of 6.0 (P <10−6) in the CAST intercross (46 mice). This QTL is responsible for 57 and 43% of ABR threshold variance, respectively, in each strain combination. In addition, a C57BL/6J congenic line carrying a 129/Ola segment encompassing the described QTL region when made homozygous for tubby also exhibits normal hearing ability. We hypothesize that C57BL/6J carries a recessive mutation of the moth1gene which interacts with the tub mutation to cause hearing loss in tub/tub mice. A moth1 allele from either AKR/J, CAST/Ei or 129/Ola is sufficient to protect C57BL/6J-tub/tubmice from hearing loss.</description><identifier>ISSN: 0964-6906</identifier><identifier>EISSN: 1460-2083</identifier><identifier>DOI: 10.1093/hmg/8.9.1761</identifier><identifier>PMID: 10441341</identifier><identifier>CODEN: HNGEE5</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Adaptor Proteins, Signal Transducing ; Animals ; Biological and medical sciences ; Chromosome Mapping ; Classical genetics, quantitative genetics, hybrids ; Cochlea - cytology ; Crosses, Genetic ; Evoked Potentials, Auditory, Brain Stem - genetics ; Fluorescent Antibody Technique ; Fundamental and applied biological sciences. Psychology ; Genetic Linkage ; Genetics of eukaryotes. Biological and molecular evolution ; Genotype ; Hearing Disorders - genetics ; Lod Score ; Mice ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Proteins - genetics ; Quantitative Trait, Heritable ; Vertebrata</subject><ispartof>Human molecular genetics, 1999-09, Vol.8 (9), p.1761-1767</ispartof><rights>1999 INIST-CNRS</rights><rights>Copyright Oxford University Press(England) Sep 1999</rights><rights>1999 Oxford University Press 1999</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4201-19157bd997e7164c4d71b0e605e4744928c1b26d70b1df8767cf0bc183b0a31e3</citedby><cites>FETCH-LOGICAL-c4201-19157bd997e7164c4d71b0e605e4744928c1b26d70b1df8767cf0bc183b0a31e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1943535$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10441341$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ikeda, Akihiro</creatorcontrib><creatorcontrib>Yin Zheng, Qing</creatorcontrib><creatorcontrib>Rosenstiel, Philip</creatorcontrib><creatorcontrib>Maddatu, Terry</creatorcontrib><creatorcontrib>Zuberi, Aamir R.</creatorcontrib><creatorcontrib>Roopenian, Derry C.</creatorcontrib><creatorcontrib>North, Michael A.</creatorcontrib><creatorcontrib>Naggert, Jürgen K.</creatorcontrib><creatorcontrib>Johnson, Kenneth R.</creatorcontrib><creatorcontrib>Nishina, Patsy M.</creatorcontrib><title>Genetic Modification of Hearing in Tubby Mice: Evidence for the Existence of a Major Gene (moth1) Which Protects Tubby Mice from Hearing Loss</title><title>Human molecular genetics</title><addtitle>Human Molecular Genetics</addtitle><description>Quantitative trait locus (QTL) analysis of genetic crosses has proven to be a useful tool for identifying loci associated with specific phenotypes and for dissecting genetic components of complex traits.Inclusion of a mutation that interacts epistatically with QTLs in genetic crosses is a unique and potentially powerful method of revealing the function of novel genes and pathways. Although we know that a mutation within the novel tubgene leads to obesity and cochlear and retinal degeneration, the biological function of the gene and the mechanism by which it induces its phenotypes are not known. In the current study, a QTL analysis for auditory brainstem response (ABR) thresholds, which indicates hearing ability, was performed in tubby mice from F2 intercrosses between C57BL/6J-tub/tub and AKR/J−+/+ F1 hybrids (AKR intercross) and between C57BL/6J-tub/ tub and CAST/Ei.B6-tub/tub F1 hybrids (CAST intercross). A major QTL, designated as modifier of tubby hearingl (mothl,) was identified on chromosome 2 with aLOD scoreof 33.4(P<10−33) in the AKR intercross (181 mice) and of 6.0 (P <10−6) in the CAST intercross (46 mice). This QTL is responsible for 57 and 43% of ABR threshold variance, respectively, in each strain combination. In addition, a C57BL/6J congenic line carrying a 129/Ola segment encompassing the described QTL region when made homozygous for tubby also exhibits normal hearing ability. We hypothesize that C57BL/6J carries a recessive mutation of the moth1gene which interacts with the tub mutation to cause hearing loss in tub/tub mice. A moth1 allele from either AKR/J, CAST/Ei or 129/Ola is sufficient to protect C57BL/6J-tub/tubmice from hearing loss.</description><subject>Adaptor Proteins, Signal Transducing</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Chromosome Mapping</subject><subject>Classical genetics, quantitative genetics, hybrids</subject><subject>Cochlea - cytology</subject><subject>Crosses, Genetic</subject><subject>Evoked Potentials, Auditory, Brain Stem - genetics</subject><subject>Fluorescent Antibody Technique</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genetic Linkage</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>Genotype</subject><subject>Hearing Disorders - genetics</subject><subject>Lod Score</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Inbred Strains</subject><subject>Proteins - genetics</subject><subject>Quantitative Trait, Heritable</subject><subject>Vertebrata</subject><issn>0964-6906</issn><issn>1460-2083</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk9v0zAYxiMEYt3gxhlZCE0gkc5v7NgxByQYpWVqxQ5DIC6W4ziNSxMPO522D8F3xqFVKVw4WfLz8-P3z5MkTwCPAQty1rTLs2IsxsAZ3EtGQBlOM1yQ-8kIC0ZTJjA7So5DWGEMjBL-MDkCTCkQCqPk59R0prcaLVxla6tVb12HXI1mRnnbLZHt0NWmLO_QwmrzGk1ubGU6bVDtPOobgya3NvS_b-IjhRZqFYXBFL1oXd_AS_SlsbpBl971RvfhwA3V3rX7j-YuhEfJg1qtg3m8O0-Szx8mV-ezdP5p-vH87TzVNMOQgoCcl5UQ3PDYkqYVhxIbhnNDOaUiKzSUGas4LqGqC864rnGpoSAlVgQMOUnebH2vN2VrKm263qu1vPa2Vf5OOmXl30pnG7l0N5JkNM40iwanOwPvfmxM6GVrgzbrteqM2wTJhMgxLvL_gsAJ5ZmgEXz2D7hyG9_FKcgMIGIEBujVFtI-Tsubel8yYDmkQcY0yEIKOaQh4k8P2zyAt-uPwPMdoIJW69qrTtvwh4t15WRoIt1iw6pv97Ly3yXjhOdy9vWbvJi_u-TvpxcSyC8SZcs7</recordid><startdate>19990901</startdate><enddate>19990901</enddate><creator>Ikeda, Akihiro</creator><creator>Yin Zheng, Qing</creator><creator>Rosenstiel, Philip</creator><creator>Maddatu, Terry</creator><creator>Zuberi, Aamir R.</creator><creator>Roopenian, Derry C.</creator><creator>North, Michael A.</creator><creator>Naggert, Jürgen K.</creator><creator>Johnson, Kenneth R.</creator><creator>Nishina, Patsy M.</creator><general>Oxford University Press</general><general>Oxford Publishing Limited (England)</general><scope>BSCLL</scope><scope>IQODW</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>7QP</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19990901</creationdate><title>Genetic Modification of Hearing in Tubby Mice: Evidence for the Existence of a Major Gene (moth1) Which Protects Tubby Mice from Hearing Loss</title><author>Ikeda, Akihiro ; Yin Zheng, Qing ; Rosenstiel, Philip ; Maddatu, Terry ; Zuberi, Aamir R. ; Roopenian, Derry C. ; North, Michael A. ; Naggert, Jürgen K. ; Johnson, Kenneth R. ; Nishina, Patsy M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4201-19157bd997e7164c4d71b0e605e4744928c1b26d70b1df8767cf0bc183b0a31e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Adaptor Proteins, Signal Transducing</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Chromosome Mapping</topic><topic>Classical genetics, quantitative genetics, hybrids</topic><topic>Cochlea - cytology</topic><topic>Crosses, Genetic</topic><topic>Evoked Potentials, Auditory, Brain Stem - genetics</topic><topic>Fluorescent Antibody Technique</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genetic Linkage</topic><topic>Genetics of eukaryotes. Biological and molecular evolution</topic><topic>Genotype</topic><topic>Hearing Disorders - genetics</topic><topic>Lod Score</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Inbred Strains</topic><topic>Proteins - genetics</topic><topic>Quantitative Trait, Heritable</topic><topic>Vertebrata</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ikeda, Akihiro</creatorcontrib><creatorcontrib>Yin Zheng, Qing</creatorcontrib><creatorcontrib>Rosenstiel, Philip</creatorcontrib><creatorcontrib>Maddatu, Terry</creatorcontrib><creatorcontrib>Zuberi, Aamir R.</creatorcontrib><creatorcontrib>Roopenian, Derry C.</creatorcontrib><creatorcontrib>North, Michael A.</creatorcontrib><creatorcontrib>Naggert, Jürgen K.</creatorcontrib><creatorcontrib>Johnson, Kenneth R.</creatorcontrib><creatorcontrib>Nishina, Patsy M.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Human molecular genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ikeda, Akihiro</au><au>Yin Zheng, Qing</au><au>Rosenstiel, Philip</au><au>Maddatu, Terry</au><au>Zuberi, Aamir R.</au><au>Roopenian, Derry C.</au><au>North, Michael A.</au><au>Naggert, Jürgen K.</au><au>Johnson, Kenneth R.</au><au>Nishina, Patsy M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic Modification of Hearing in Tubby Mice: Evidence for the Existence of a Major Gene (moth1) Which Protects Tubby Mice from Hearing Loss</atitle><jtitle>Human molecular genetics</jtitle><addtitle>Human Molecular Genetics</addtitle><date>1999-09-01</date><risdate>1999</risdate><volume>8</volume><issue>9</issue><spage>1761</spage><epage>1767</epage><pages>1761-1767</pages><issn>0964-6906</issn><eissn>1460-2083</eissn><coden>HNGEE5</coden><abstract>Quantitative trait locus (QTL) analysis of genetic crosses has proven to be a useful tool for identifying loci associated with specific phenotypes and for dissecting genetic components of complex traits.Inclusion of a mutation that interacts epistatically with QTLs in genetic crosses is a unique and potentially powerful method of revealing the function of novel genes and pathways. Although we know that a mutation within the novel tubgene leads to obesity and cochlear and retinal degeneration, the biological function of the gene and the mechanism by which it induces its phenotypes are not known. In the current study, a QTL analysis for auditory brainstem response (ABR) thresholds, which indicates hearing ability, was performed in tubby mice from F2 intercrosses between C57BL/6J-tub/tub and AKR/J−+/+ F1 hybrids (AKR intercross) and between C57BL/6J-tub/ tub and CAST/Ei.B6-tub/tub F1 hybrids (CAST intercross). A major QTL, designated as modifier of tubby hearingl (mothl,) was identified on chromosome 2 with aLOD scoreof 33.4(P<10−33) in the AKR intercross (181 mice) and of 6.0 (P <10−6) in the CAST intercross (46 mice). This QTL is responsible for 57 and 43% of ABR threshold variance, respectively, in each strain combination. In addition, a C57BL/6J congenic line carrying a 129/Ola segment encompassing the described QTL region when made homozygous for tubby also exhibits normal hearing ability. We hypothesize that C57BL/6J carries a recessive mutation of the moth1gene which interacts with the tub mutation to cause hearing loss in tub/tub mice. A moth1 allele from either AKR/J, CAST/Ei or 129/Ola is sufficient to protect C57BL/6J-tub/tubmice from hearing loss.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>10441341</pmid><doi>10.1093/hmg/8.9.1761</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; EZB-FREE-00999 freely available EZB journals |
| subjects | Adaptor Proteins, Signal Transducing Animals Biological and medical sciences Chromosome Mapping Classical genetics, quantitative genetics, hybrids Cochlea - cytology Crosses, Genetic Evoked Potentials, Auditory, Brain Stem - genetics Fluorescent Antibody Technique Fundamental and applied biological sciences. Psychology Genetic Linkage Genetics of eukaryotes. Biological and molecular evolution Genotype Hearing Disorders - genetics Lod Score Mice Mice, Inbred C57BL Mice, Inbred Strains Proteins - genetics Quantitative Trait, Heritable Vertebrata |
| title | Genetic Modification of Hearing in Tubby Mice: Evidence for the Existence of a Major Gene (moth1) Which Protects Tubby Mice from Hearing Loss |
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