Rodent genetic models of Huntington disease

The Ventral Striatopallidum and Extended Amygdala in Huntington Disease

“…From the third week after birth, R6/2 mice develop an early phenotype with severe behavioral and motor dysfunctions. Tremors, lack of coordination and enormous loss of weight is accompanied by a severe general atrophy of the brain leading finally to death within 12 -15 weeks of age (Crook & Housman, 2011;Heng et al, 2008). The R6/2 mice show an early and overall distribution of htt aggregates in many brain areas including the hippocampus, the cerebellum and the spinal cord as detected by the EM48 antibody .…”

The importance of integrating basic and clinical research toward the development of new therapies for Huntington disease

“…Disease progression in the R6/2 mouse is rapid and recapitulates some of the pathological findings in postmortem HD tissues, including inclusion formation, some striatal and cortical neuronal death, ventricular enlargement, widespread white matter atrophy, and similar patterns of transcriptional dysregulation (21,(23)(24)(25)(26)(27)(28). Other full-length models of HD include knockin mouse models (19,26) and transgenic YAC and BAC mice and rats (20,29,30). These differ in mHTT expression levels, length of the CAG repeat, age of phenotype onset, rate of disease progression, extent of neuronal death, and the robustness of behavioral (cognitive, psychiatric, and motor) disturbances.…”

“…Identifying mutations causative for a given disease enables the development of genetic animal models; there are now many rodent models of HD, and sheep and primate models have been engineered more recently (17)(18)(19)(20). The R6/2 mouse is the most widely used and expresses an N-terminal fragment of the HTT gene under the control of the human HTT promoter (21).…”

Review article Genetically modified animals for use in research and biotechnology

“…With the advance of genetic engineering, it was no longer necessary to wait; these animals could be produced with the desired alterations, since the genetic causes of the disease in question were known. So, animals were produced that serve as models for studies of different types of cancers (Santos et al, 2008), heart disease (Moon, 2008), hypertension (Zadelaar et al, 2007), diabetes (Leroith and Gavrilova, 2006), obesity (Blüher, 2005), osteoporosis (Klein, 2008), glaucoma (Zhou et al, 2008), blindness (Moussaif et al, 2006), deafness (Leibovici et al, 2008), Huntington's syndrome (Heng et al, 2008), Down's syndrome (Patterson, 2009), Parkinson's disease (Harvey et al, 2008), Alzheimer's disease (Gotz et al, 2009), anxiety (Kalueff et al, 2007, and depression (Kalueff et al, 2007).…”