Variability and modification of the symptoms of Huntington’s disease (HD) are commonly observed in both patient populations and animal models of the disease. Utilizing a stable line of the R6/2 HD mouse model, the present study investigated the role of genetic background in the onset and severity of HD symptoms in a transgenic mouse. R6/2 congenic C57BL/6J and C57BL/6J×DBA/2J F1 (B6D2F1) mice were evaluated for survival and a number of behavioral phenotypes. This study reports that the presence of the DBA/2J allele results in amelioration or exacerbation of several HD-like phenotypes characteristic of the R6/2 mouse model and indicates the presence of dominant genetic modifiers of HD symptoms. This study is the first step in identifying genes that confer natural genetic variation and modify the HD symptoms. This identification may lead to novel targets for treatment and help elucidate the molecular mechanisms of HD pathogenesis.
Variability and modification of the symptoms of Huntington’s disease (HD) are commonly observed in both pan class="Species">patient populations and animal models of the disease. Utilizing a stable line of the R6/2 HDmouse model, the present study investigated the role of genetic background in the onset and severity of HD symptoms in a transgenicmouse. R6/2 congenic C57BL/6J and C57BL/6J×DBA/2J F1 (B6D2F1) mice were evaluated for survival and a number of behavioral phenotypes. This study reports that the presence of the DBA/2J allele results in amelioration or exacerbation of several HD-like phenotypes characteristic of the R6/2 mouse model and indicates the presence of dominant genetic modifiers of HD symptoms. This study is the first step in identifying genes that confer natural genetic variation and modify the HD symptoms. This identification may lead to novel targets for treatment and help elucidate the molecular mechanisms of HD pathogenesis.
Authors: L Mangiarini; K Sathasivam; M Seller; B Cozens; A Harper; C Hetherington; M Lawton; Y Trottier; H Lehrach; S W Davies; G P Bates Journal: Cell Date: 1996-11-01 Impact factor: 41.582
Authors: J N Crawley; J K Belknap; A Collins; J C Crabbe; W Frankel; N Henderson; R J Hitzemann; S C Maxson; L L Miner; A J Silva; J M Wehner; A Wynshaw-Boris; R Paylor Journal: Psychopharmacology (Berl) Date: 1997-07 Impact factor: 4.530
Authors: Joana Branco; Ismael Al-Ramahi; Lubna Ukani; Alma M Pérez; Pedro Fernandez-Funez; Diego Rincón-Limas; Juan Botas Journal: Hum Mol Genet Date: 2007-11-05 Impact factor: 6.150
Authors: L Djoussé; B Knowlton; M Hayden; E W Almqvist; R Brinkman; C Ross; R Margolis; A Rosenblatt; A Durr; C Dode; P J Morrison; A Novelletto; M Frontali; R J A Trent; E McCusker; E Gómez-Tortosa; D Mayo; R Jones; A Zanko; M Nance; R Abramson; O Suchowersky; J Paulsen; M Harrison; Q Yang; L A Cupples; J F Gusella; M E MacDonald; R H Myers Journal: Am J Med Genet A Date: 2003-06-15 Impact factor: 2.802
Authors: Javier Gayán; Denise Brocklebank; J Michael Andresen; Gorka Alkorta-Aranburu; M Zameel Cader; Simone A Roberts; Stacey S Cherny; Nancy S Wexler; Lon R Cardon; David E Housman Journal: Genet Epidemiol Date: 2008-07 Impact factor: 2.135
Authors: Nancy S Wexler; Judith Lorimer; Julie Porter; Fidela Gomez; Carol Moskowitz; Edith Shackell; Karen Marder; Graciela Penchaszadeh; Simone A Roberts; Javier Gayán; Denise Brocklebank; Stacey S Cherny; Lon R Cardon; Jacqueline Gray; Stephen R Dlouhy; Sandra Wiktorski; Marion E Hodes; P Michael Conneally; Jack B Penney; James Gusella; Jang-Ho Cha; Michael Irizarry; Diana Rosas; Steven Hersch; Zane Hollingsworth; Marcy MacDonald; Anne B Young; J Michael Andresen; David E Housman; Margot Mieja De Young; Ernesto Bonilla; Theresa Stillings; Americo Negrette; S Robert Snodgrass; Maria Dolores Martinez-Jaurrieta; Maria A Ramos-Arroyo; Jacqueline Bickham; Juan Sanchez Ramos; Frederick Marshall; Ira Shoulson; Gustavo J Rey; Andrew Feigin; Norman Arnheim; Amarilis Acevedo-Cruz; Leticia Acosta; Jose Alvir; Kenneth Fischbeck; Leslie M Thompson; Angela Young; Leon Dure; Christopher J O'Brien; Jane Paulsen; Adam Brickman; Denise Krch; Shelley Peery; Penelope Hogarth; Donald S Higgins; Bernhard Landwehrmeyer Journal: Proc Natl Acad Sci U S A Date: 2004-03-01 Impact factor: 11.205
Authors: H Telenius; H P Kremer; J Theilmann; S E Andrew; E Almqvist; M Anvret; C Greenberg; J Greenberg; G Lucotte; F Squitieri Journal: Hum Mol Genet Date: 1993-10 Impact factor: 6.150
Authors: Liliana Menalled; Bassem F El-Khodor; Monica Patry; Mayte Suárez-Fariñas; Samantha J Orenstein; Benjamin Zahasky; Christina Leahy; Vanessa Wheeler; X William Yang; Marcy MacDonald; A Jennifer Morton; Gill Bates; Janet Leeds; Larry Park; David Howland; Ethan Signer; Allan Tobin; Daniela Brunner Journal: Neurobiol Dis Date: 2009-05-21 Impact factor: 5.996
Authors: Melissa K Strong; Amber L Southwell; Jennifer M Yonan; Michael R Hayden; Grant R Macgregor; Leslie M Thompson; Oswald Steward Journal: J Huntingtons Dis Date: 2012
Authors: Ricardo Mouro Pinto; Ella Dragileva; Andrew Kirby; Alejandro Lloret; Edith Lopez; Jason St Claire; Gagan B Panigrahi; Caixia Hou; Kim Holloway; Tammy Gillis; Jolene R Guide; Paula E Cohen; Guo-Min Li; Christopher E Pearson; Mark J Daly; Vanessa C Wheeler Journal: PLoS Genet Date: 2013-10-31 Impact factor: 5.917
Authors: Jingyu Liu; Jennifer Ciarochi; Vince D Calhoun; Jane S Paulsen; H Jeremy Bockholt; Hans J Johnson; Jeffrey D Long; Dongdong Lin; Flor A Espinoza; Maria B Misiura; Arvind Caprihan; Jessica A Turner Journal: Front Neurol Date: 2018-03-29 Impact factor: 4.003
Authors: Stéphanie Tomé; Kevin Manley; Jodie P Simard; Greg W Clark; Meghan M Slean; Meera Swami; Peggy F Shelbourne; Elisabeth R M Tillier; Darren G Monckton; Anne Messer; Christopher E Pearson Journal: PLoS Genet Date: 2013-02-28 Impact factor: 5.917