Progeria Model Customization Services

Progeria, specifically Hutchinson-Gilford Progeria Syndrome (HGPS), is caused by mutations in the LMNA gene, leading to the production of progerin, a toxic form of the lamin A protein. This results in premature aging symptoms such as growth failure, cardiovascular disease, and skin abnormalities. In addition to modeling classical HGPS, progeria models are instrumental in elucidating pathways relevant to broader aging syndromes, including mandibuloacral dysplasia and atypical Werner syndrome.

Fig. 1 Lmna^G609G knock-in mice show abnormal body posture with a marked cervicothoracic lordokyphosis, together with a progressive loss of weight. (Mayora P, et al., 2018)

CD BioSciences offers progeria model customization services to support pharmaceutical companies and academic laboratories in the discovery and development of anti-aging drug candidates.

Custom Mouse Models of Progeria

Our company provides an extensive collection of genetically engineered mouse models that recapitulate the molecular and pathological features of HGPS. Our team supports the generation, breeding, and phenotypic validation of these models for aging research.

• Lmna^HG/+ mice. We offer Lmna^HG/+ mice carrying the equivalent mutation found in human HGPS (c.1824C>T), which activates a cryptic splice site in exon 11 of the Lmna gene. These mice exhibit mild progeroid features, including vascular abnormalities, kyphosis, reduced subcutaneous fat, and skin defects.
• Lmna^G609G/G609G mice. We provide Lmna^G609G/G609G mice, a widely used mouse model of HGPS. This homozygous point mutation (c.1827C>T) activates an aberrant splicing in the Lmna gene, resulting in the production of progerin, a truncated form of lamin A that closely mimics the pathogenic mechanism of the human G609G mutation.
• Zmpste24^-/- mice. The Zmpste24 gene encodes a zinc metalloproteinase essential for the final cleavage step in lamin A maturation. We provide Zmpste24^-/- mice to mimic HGPS-like defects in nuclear morphology and systemic aging.
• HGPS^rev mice. Our company offers HGPS^rev mice, which express progerin in a temporally and spatially controlled manner. The model integrates a loxP-stop-loxP (LSL) cassette upstream of progerin under a ubiquitous or tissue-specific promoter, activated by Cre recombinase. Upon Cre activation, mice rapidly develop HGPS-like phenotypes in specific tissues (e.g., vascular endothelium, smooth muscle, adipose tissue).

Custom Minipig Models of Progeria

Given their anatomical, cardiovascular, and metabolic similarities to humans, minipigs serve as a valuable model for progeria research. At CD BioSciences, our experts employ gene editing strategies to generate LMNA knock-in minipigs. These customized progeria models exhibit key disease phenotypes, including growth impairment, vascular fibrosis, dermal thinning, and osteolytic lesions.

Characterization of Progeria Models

• Phenotype validation services. We help clients assess hallmark features of progeria models, such as growth retardation, vascular fibrosis, dermal thinning, and osteolytic lesions, validating whether the models reflect progeria pathophysiology.
• Molecular and cellular analysis services. Our experts quantify LMNA expression, nuclear morphology, DNA damage markers, and progerin accumulation, offering mechanistic insights and supporting target validation for candidate therapeutics.

By offering custom mouse and minipig models of progeria, CD BioSciences provides researchers with the tools necessary to explore the intricacies of progeria and develop effective anti-aging drugs. If you are interested in our services, please feel free to contact us or make an online inquiry.

References

1. Dorado B, et al. Generation and characterization of a novel knock-in minipig model of Hutchinson-Gilford progeria syndrome. Cell Discov, 2019, 5:16.
2. Mayora P, et al. Progeria Mouse Models. Conn's Handbook of Models for Human Aging, 2018.