HD Mouse Models

Mouse models of Huntington's disease (HD) are critical to the development of our understanding of gene expression changes in this disease, and to elucidate the relationship between gene expression and behavior. Creative Biolabs' scientists have extensive experience and excellent skills in the field of neuroscience. Our goal is to provide our customers with affordable development services and reliable results.

About HD

HD is an autosomal dominant neurodegenerative disorder, resulting in expansion of the CAG repeat in exon 1 of the HTT gene. It is a devastating illness that usually strikes between the ages of 35 and 45. The disease is transmitted in an autosomal dominant manner and is caused by an expansion of a CAG repeat region in the gene encoding huntingtin, a protein of unknown function.

Mouse Models of HD

HD mouse models have allowed mutant and wild-type huntingtin (Htt) expression and gene manipulation, the CAG repeat length, the size of protein fragments inserted into the genome, and the effects of stable and induced expression.

• Transgenic Models

The earliest and most thoroughly characterized mouse models of HD are the R6 lines, R6/1, and R6/2. Both transgenic models were developed from the same transgenic insert, using a 1.9 KB 5 'end fragment of the human HTT gene. The R6/1 model expresses around 115 CAG repeats, whereas the original R6/2 mice carried a larger repeat length of 141-157. Both R6 models exhibit progressive dyskinesia, gait abnormalities, and involuntary, rigid movements reminiscent of the effects seen in human HD. Three further transgenic mouse models of HD have also been developed expressing full-length human Htt, (HD48 and HD89) or the first 171 amino acids of human Htt (N171-Q82).

• Knock-in Models

Several knock-in mouse models of HD have been developed with a wide range in the number of CAG repeats expressed. These models have the advantage over transgenic mice that the expressed genes are endogenous murine HD homologue genes with extended CAG repeats and therefore also use murine native promoters, making them more suitable for studying HD molecular pathology and behavioral phenotypic development from birth. The first knock-in model to be developed was the HdhQ50, which more closely models the number of CAG repeats found in human HD. The two most widely utilized knock-in mouse models of HD are the HdhQ111 and HdhQ150, with 111 and 150 CAG repeats, respectively.

• Inducible Models

Two inducible mouse models of HD have been developed using exon 1 of human HTT; one with 94 CAG repeats, and a more recent model with 148 repeats. In addition to their similarity to other HD transgenic models, what is exciting and valuable about these models is their ability to cancel the expression of mHtt transgenic.

Fig.1 Comparison of phenotypes between transgenic and knock-in mouse models of HD and human patients. (Ehrnhoefer, 2009)

Gene expression studies in mouse models of HD, as well as other diseases, are imperative for the advancement of our knowledge of neurodegenerative disease mechanisms. Understanding the pathogenesis will help identify new targets for therapeutic interventions. Creative Biolabs has 15+ years of experience providing CRO services. We are one of the US's leading providers to pharma, bioscience, and contract research organizations for flexible and professional custom-tailored study design of HD mouse models. If you are interested in our HD mouse models-related services, please feel free to contact us for more.

Reference

1. Ehrnhoefer, D.E.; et al. Mouse models of Huntington disease: variations on a theme. Disease models & mechanisms. 2009, 2 (3-4): 123-129.