Coat Color-Facilitated Efficient Generation and Analysis of a Mouse Model of Down Syndrome Triplicated for All Human Chromosome 21 Orthologous Regions
Down syndrome (DS) is one of the most complex genetic disorders in humans and a leading genetic cause of developmental delays and intellectual disabilities. The mouse remains an essential model organism in DS research because human chromosome 21 (Hsa21) is orthologously conserved with three regions...
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MDPI AG
2021-08-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/12/8/1215 |
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| author | Yichen Li Zhuo Xing Tao Yu Annie Pao Marcel Daadi Y. Eugene Yu |
| author_facet | Yichen Li Zhuo Xing Tao Yu Annie Pao Marcel Daadi Y. Eugene Yu |
| author_sort | Yichen Li |
| collection | DOAJ |
| description | Down syndrome (DS) is one of the most complex genetic disorders in humans and a leading genetic cause of developmental delays and intellectual disabilities. The mouse remains an essential model organism in DS research because human chromosome 21 (Hsa21) is orthologously conserved with three regions in the mouse genome. Recent studies have revealed complex interactions among different triplicated genomic regions and Hsa21 gene orthologs that underlie major DS phenotypes. Because we do not know conclusively which triplicated genes are indispensable in such interactions for a specific phenotype, it is desirable that all evolutionarily conserved Hsa21 gene orthologs are triplicated in a complete model. For this reason, the Dp(10)1Yey/+;Dp(16)1Yey/+;Dp(17)1Yey/+ mouse is the most complete model of DS to reflect gene dosage effects because it is the only mutant triplicated for all Hsa21 orthologous regions. Recently, several groups have expressed concerns that efforts needed to generate the triple compound model would be so overwhelming that it may be impractical to take advantage of its unique strength. To alleviate these concerns, we developed a strategy to drastically improve the efficiency of generating the triple compound model with the aid of a targeted coat color, and the results confirmed that the mutant mice generated via this approach exhibited cognitive deficits. |
| first_indexed | 2024-03-10T08:47:54Z |
| format | Article |
| id | doaj.art-8cf913f23a6c4242baab564845311b33 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T08:47:54Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-8cf913f23a6c4242baab564845311b332023-11-22T07:46:11ZengMDPI AGGenes2073-44252021-08-01128121510.3390/genes12081215Coat Color-Facilitated Efficient Generation and Analysis of a Mouse Model of Down Syndrome Triplicated for All Human Chromosome 21 Orthologous RegionsYichen Li0Zhuo Xing1Tao Yu2Annie Pao3Marcel Daadi4Y. Eugene Yu5The Children’s Guild Foundation Down Syndrome Research Program, Genetics and Genomics Program and Department of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USAThe Children’s Guild Foundation Down Syndrome Research Program, Genetics and Genomics Program and Department of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USAThe Children’s Guild Foundation Down Syndrome Research Program, Genetics and Genomics Program and Department of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USAThe Children’s Guild Foundation Down Syndrome Research Program, Genetics and Genomics Program and Department of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USARegenerative Medicine and Aging Unit, Texas Biomedical Research Institute, Long School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78245, USAThe Children’s Guild Foundation Down Syndrome Research Program, Genetics and Genomics Program and Department of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USADown syndrome (DS) is one of the most complex genetic disorders in humans and a leading genetic cause of developmental delays and intellectual disabilities. The mouse remains an essential model organism in DS research because human chromosome 21 (Hsa21) is orthologously conserved with three regions in the mouse genome. Recent studies have revealed complex interactions among different triplicated genomic regions and Hsa21 gene orthologs that underlie major DS phenotypes. Because we do not know conclusively which triplicated genes are indispensable in such interactions for a specific phenotype, it is desirable that all evolutionarily conserved Hsa21 gene orthologs are triplicated in a complete model. For this reason, the Dp(10)1Yey/+;Dp(16)1Yey/+;Dp(17)1Yey/+ mouse is the most complete model of DS to reflect gene dosage effects because it is the only mutant triplicated for all Hsa21 orthologous regions. Recently, several groups have expressed concerns that efforts needed to generate the triple compound model would be so overwhelming that it may be impractical to take advantage of its unique strength. To alleviate these concerns, we developed a strategy to drastically improve the efficiency of generating the triple compound model with the aid of a targeted coat color, and the results confirmed that the mutant mice generated via this approach exhibited cognitive deficits.https://www.mdpi.com/2073-4425/12/8/1215Down syndromemouse modelscoat colorscognitive function |
| spellingShingle | Yichen Li Zhuo Xing Tao Yu Annie Pao Marcel Daadi Y. Eugene Yu Coat Color-Facilitated Efficient Generation and Analysis of a Mouse Model of Down Syndrome Triplicated for All Human Chromosome 21 Orthologous Regions Genes Down syndrome mouse models coat colors cognitive function |
| title | Coat Color-Facilitated Efficient Generation and Analysis of a Mouse Model of Down Syndrome Triplicated for All Human Chromosome 21 Orthologous Regions |
| title_full | Coat Color-Facilitated Efficient Generation and Analysis of a Mouse Model of Down Syndrome Triplicated for All Human Chromosome 21 Orthologous Regions |
| title_fullStr | Coat Color-Facilitated Efficient Generation and Analysis of a Mouse Model of Down Syndrome Triplicated for All Human Chromosome 21 Orthologous Regions |
| title_full_unstemmed | Coat Color-Facilitated Efficient Generation and Analysis of a Mouse Model of Down Syndrome Triplicated for All Human Chromosome 21 Orthologous Regions |
| title_short | Coat Color-Facilitated Efficient Generation and Analysis of a Mouse Model of Down Syndrome Triplicated for All Human Chromosome 21 Orthologous Regions |
| title_sort | coat color facilitated efficient generation and analysis of a mouse model of down syndrome triplicated for all human chromosome 21 orthologous regions |
| topic | Down syndrome mouse models coat colors cognitive function |
| url | https://www.mdpi.com/2073-4425/12/8/1215 |
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