No, the zQ175 knock-in model does not carry the full human HTT gene. Instead, it contains a partially humanized allele in which mouse exon 1 is replaced by human HTT exon 1 with an expanded ~180 CAG repeat. The remainder of the gene is still of mouse origin, and the protein produced is a chimeric full-length mutant huntingtin.  

This design is sufficient for faithfully modelling many key aspects of Huntington’s disease pathology, including age-dependent behavioural deficits, mutant huntingtin aggregation. 

However, the gene sequence limitation means that the zQ175 model does not fully replicate the entire human HTT genotype. This is particularly relevant for gene therapy and antisense oligonucleotide (ASO) programs targeting full-length human HTT transcripts, where models carrying the complete human HTT gene may be more suitable.  

At InnoSer, we understand these distinctions and can advise on alternative or complementary HD models for gene-targeting studies. Reach out to our team to discuss the most appropriate Huntington’s disease mouse model for your therapeutic approach.  

Heterozygous zQ175 mice are generally preferred for modeling Huntington’s disease, as on the genetic level, they mirror the typical patient genotype with one mutant htt allele. They exhibit progressive behavioral, molecular, and anatomical changes, making them highly suitable for efficacy studies. 

Homozygous zQ175 mice develop more pronounced and earlier-onset phenotypes. While less representative of the patients’ genetic makeup, they are valuable for accelerated proof-of-concept studies or when a strong disease readout is required within a shorter timeframe.  

At InnoSer, we have extensively profiled both heterozygous and homozygous zQ175 mice across behavioral, molecular, anatomical, and metabolic domains (view comparison table here), and can advise on the most appropriate genotype for your specific study goals. Reach out to our team to discuss the most appropriate genotype for your study now. 

In heterozygous zQ175 mice, molecular and electrophysiological alterations (e.g., DARPP-32 downregulation, synaptic deficits) can be detected as early as 3–4 months of age. Behavioral deficits, such as reduced open field activity or rotarod performance, typically become apparent between 4–6 months. In homozygous animals, phenotypic changes may occur earlier and more robustly due to higher gene dosage.  

Yes, scientists at InnoSer have characterized and observed sex differences in the zQ175 mouse model and, therefore, sex should be considered as a variable during study planning. Our historical validation datasets include both male and female cohorts.  

Forelimb grip strength deficits, for example, are sex- and age-dependent: 

• In homozygous male zQ175 mice, motor impairments were detectable as early as 3.5 months. 

• In female mice, a comparable reduction in grip strength was only observed at 8.7 months. 

Contact our team to obtain the full validation data sets or to plan a study that accounts for sex as a biological variable. 

Metabolic dysfunction is a known feature of Huntington’s disease, observed in both preclinical models and human patients. Huntington’s Disease patients often display altered energy metabolism and insulin sensitivity. In the zQ175 model, we observe similar disruptions in glucose handling and insulin levels, especially at later disease stages.

These metabolic readouts support the model’s clinical translatability and offer valuable endpoints for therapies targeting systemic or peripheral Huntington’s disease manifestations. Reach out to our team to discuss including alternative metabolic readouts such as plasma and insulin assessment when running nonclinical efficacy studies using the zQ175 mouse model.