Progeria refers to a group of genetic disorders characterized by accelerated aging across multiple body systems. Based on different causative genes, progeroid syndromes are classified into various types:
- Some are caused by mutations in genes encoding DNA repair proteins, such as Werner Syndrome (WS), Bloom Syndrome (BS), and Cockayne Syndrome (CS).
- Others are linked to mutations in genes encoding nuclear lamins or processing enzymes, such as Hutchinson-Gilford Progeria Syndrome (HGPS) and Restrictive Dermopathy (RD).
HGPS is the most intensively studied and representative progeroid syndrome, serving as a key model in aging research. HGPS is a rare genetic disease caused by a point mutation in the LMNA gene. The global incidence is approximately 1 in 4–8 million newborns. Affected infants appear normal at birth but rapidly develop distinctive clinical characterization:
severe growth retardation, total alopecia, loss of subcutaneous fat and skeletal muscle, skin atrophy, joint stiffness, reduced bone mineral density, and vision loss.
With age, patients develop atherosclerosis, skeletal deformities, and cardiovascular diseases. The average lifespan is 14.6 years, with death caused by stroke, myocardial infarction, heart failure, or atherosclerosis.
Pathogenesis
HGPS is caused by a C1824T point mutation (cytosine to thymine) in exon 11 of the LMNA gene. This mutation activates a cryptic splice site, leading to abnormal pre-mRNA splicing and production of a transcript lacking 150 base pairs.
The transcript encodes a truncated form of lamin A called progerin. Progerin accumulates in the nucleus, disrupts nuclear envelope structure, causes abnormal nuclear morphology, and reduces mechanical stability. It also interferes with chromatin remodeling and histone modification, leading to dysregulated gene expression. Furthermore, progerin activates the p53 pathway, inducing cell cycle arrest, apoptosis, and genome instability. These cellular abnormalities ultimately lead to tissue dysfunction and systemic premature aging.
Gene Therapy
1. Antisense Oligonucleotide (ASO) Therapy
ASOs bind specific nucleotide sequences to inhibit mRNA translation, block pathogenic LMNA splicing, and suppress progerin expression. In Lmna<sup>G609G/G609G</sup> progeria mice, ASO treatment significantly reduced progerin levels, improved histopathology, and extended lifespan.
2. Adenine Base Editing (ABE) Therapy
Adenine Base Editors (ABEs) convert A·T base pairs to G·C without inducing double-strand breaks, enabling precise mutation correction. In HGPS, ABE corrects the pathogenic LMNA mutation, restores normal RNA splicing, and reduces progerin. In mouse models, ABE improved vascular health, extended lifespan from 215 to 510 days, and enhanced overall vitality.
3. Gene Editing Therapy
In situ precision gene editing directly repairs the LMNA mutation, potentially blocking progerin production at the source. Correction of the single-point mutation significantly improves cardiovascular function and survival in HGPS mice.
4. Telomerase Therapy
Recent studies show that elevated expression of the telomere protein TRF1 plus intermittent induction of OSKM reprogramming factors effectively reverses aging phenotypes and extends mouse lifespan by ~30%, without increased tumor incidence.
AAV-mediated telomerase delivery appears safe and feasible in adult/aged animals.
Mouse Models
1. Lamin A 1827C>T Mouse (Lamin A Progeria Mouse)
This progeria mouse model is established by introducing a point mutation in the Lmna gene, which activates a cryptic splice site in exon 11 (G608G: GGC→GGT). This results in the deletion of 50 amino acid residues at the C‑terminus of prelamin A, generating a truncated form known as progerin. Progerin retains the CXXA domain but lacks the ZMPSTE24 cleavage site, preventing C‑terminal processing. As a result, the exposed farnesylcysteine methyl ester remains permanently attached. Over time, the accumulation of progerin causes a series of cellular defects and dysfunctions, ultimately leading to cellular and tissue senescence.
MingCeler has introduced the Lmna point mutation into mice via gene targeting, in which nucleotide 1827 of the mouse Lmna gene is changed from cytosine (C) to thymine (T), generating a reliable progeria mouse model. Both heterozygous and homozygous mutant mice exhibit obvious accelerated aging phenotypes, including: alopecia, skeletal abnormalities, impaired motor function, growth retardation, small body size, lipodystrophy, tissue and organ fibrosis, chronic inflammation, and vascular sclerosis. This model features a short lifespan and distinct aging phenotypes, making it ideal for mechanistic research and new drug research and development of aging‑related diseases. It is a well‑recognized mouse model that recapitulates human Hutchinson‑Gilford progeria syndrome (HGPS).
2. Zmpste24⁻/⁻ Mouse
Zmpste24 is a zinc metalloprotease responsible for processing prelamin A into mature lamin A. Knockout (KO) of Zmpste24 causes prelamin A accumulation, nuclear structural defects, DNA damage, and cellular senescence. The phenotype closely mimics human HGPS and is widely used to study prelamin A‑mediated pathogenesis.
3. HLAS Mouse Model
A laminopathy model based on modified Lmna or its processing enzymes, suitable for studying tissue‑specific pathology of progerin.
MingCeler Empowers Gene Therapy R&D
Gene therapy for rare diseases relies on validated animal modeling.
MingCeler has developed a series of rare disease mouse models using proprietary TurboMice™ Technology (tetraploid complementation technology).
TurboMice™ overcomes long timelines and low success rates of conventional methods, enabling in situ precision gene editing at nearly any locus.
We generate homozygous mice directly from embryonic stem cells (ESCs) in as fast as 2 months, with no allelic segregation distress.
MingCeler offers in-stock QuickMice™ Lamin A progeria mice and custom HGPS mouse models including:
- Lamin A progeria mice
- Zmpste24⁻/⁻ mice
- HLAS mice
- more+
Welcome to inquire about model customization.
QuickMice™ Lamin A Progeria Mouse
Strain Name
C57BL/6J-LmnaTm1/MC
Strain Advantages
- Short lifespan
- Good uniformity with clear genetic background
- Clear progeria phenotype
- Suitable for a variety of aging models
Application Areas
- Mechanism research of aging-related diseases
- R&D of anti-aging products
Validation Data
Fig1. Survival curve of progeria mice
Fig2. Obvious body size difference between 3-month-old Lamin A progeria mice and 3-month-old wild-type (WT) mice.
Fig3. SA-βgal expression in the hippocampus: Significantly higher in aged mice and MingCeler Lamin A progeria mice than in young mice.
Advantages of MingCeler Mouse Model Services
- Ultrafast: Fully homozygous mice in ~2 months; F0 generation ready for experiments
- Accurate: In situ precision gene editing at ESC level with high tissue specificity
- Efficient: No chimeric mice; maintain genetic integrity; monoclonal origin
- Multi‑choice: Flexible strain selection (C57BL/6, Balb/c, ICR, etc.)
Supported by EnhancerPlus Analysis Platform and efficient tetraploid platform, MingCeler supports multi-locus gene editing, long fragment gene editing, and flexible targeting design.