huLMNA Mouse

Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic disease characterized by accelerated aging and premature death. Patients with HGPS exhibit rapid organ degeneration and physiological decline beginning in early infancy due to gene mutations. The rate of aging in HGPS patients is 5-10 times faster than in healthy individuals. This disease presents with marked hormonal abnormalities and affected children often exhibit stunted growth, baldness, limited joint mobility, and osteoporosis. Other key abnormalities include prominent scalp veins, delayed tooth eruption, impaired sexual maturation, and a low-pitched voice. Most affected children succumb to cardiovascular disease or stroke due to the rapid development of atherosclerosis ^[1]. HGPS is typically caused by a dominant-negative mutation in the LMNA gene. The LMNA gene encodes lamin A/C, a member of the nuclear lamina protein family. This highly conserved protein family forms a network layer attached to the inner nuclear membrane of eukaryotic cell nuclei. Nuclear lamina proteins play essential roles in maintaining cell structure, facilitating mitosis, and ensuring proper chromosome organization ^[2]. Mutations in the LMNA gene can lead to a spectrum of disorders, including neuromuscular diseases, heart disease, and HGPS ^[3].

LMNA-targeted drug development is still in its early stages, with preclinical studies of related drug pipelines ongoing. Gene therapy approaches targeting the LMNA gene have emerged, including antisense oligonucleotide (ASO) drugs and CRISPR gene editing technology. In vivo studies of these therapies have primarily utilized Lmna^G609G/G609G mice as a disease model for efficacy evaluation ^[1-2]. Preclinical research relies heavily on in vivo studies. Nucleic acid-based and CRISPR gene editing-based HGPS therapies target the human LMNA gene. Developing genetically humanized mouse models will accelerate the progression of gene therapy drug pipelines into clinical trials ^[4].

This strain represents a mouse Lmna gene humanized model, in which the mouse Lmna gene is replaced by the human LMNA gene, including the 3'UTR. It can be employed to investigate the pathogenesis of neuromuscular diseases, heart disease, HGPS, and other disorders, as well as for preclinical evaluation of therapeutic drugs. Homozygous huLMNA mice are viable and fertile. Additionally, based on Cyagen's proprietary TurboKnockout fusion BAC recombination technology, hot mutation models can be generated from this strain, and tailored services for specific mutations can be provided to meet the experimental needs in pharmacology and other HGPS-related fields.