In Vivo Model Development for Spinal Muscular Atrophy

Protheragen offers comprehensive in vivo animal model development services tailored for Spinal Muscular Atrophy (SMA) research and preclinical drug evaluation. Leveraging advanced genetic engineering and rigorous validation, our team provides a diverse suite of SMA models across multiple species to facilitate the rapid and reliable translation of candidate therapeutics from bench to bedside.

Spinal Muscular Atrophy (SMA) is a severe neuromuscular disorder characterized by the progressive degeneration of motor neurons, primarily caused by mutations or deletions in the SMN1 gene. Robust animal models are essential for elucidating disease mechanisms and evaluating the efficacy of novel treatments. At Protheragen, we employ a range of species—including Danio rerio (zebrafish), Drosophila melanogaster (fruit fly), and multiple strains of Mus musculus (mouse)—each offering unique advantages in modeling the genetic and pathological features of human SMA. Our models encompass knockout, mutated, and transgenic variants of SMN genes, faithfully recapitulating the human disease phenotype and enabling high-throughput screening, mechanistic studies, and therapeutic assessment.

Genetic Models

Genetic models are established by introducing targeted mutations, deletions, or transgenes into the genome to mimic the genetic basis of SMA. This includes SMN1 knockout mice, SMN2 transgenic lines, and models with specific mutations (e.g., Delta7-SMN, Khc in Drosophila). The methodology involves CRISPR/Cas9 gene editing, homologous recombination, or transgenic overexpression. Key advantages include high construct validity, reproducibility, and the ability to recapitulate disease onset and progression as seen in patients. These models are indispensable for mechanistic studies, biomarker discovery, and preclinical efficacy testing of gene therapies, antisense oligonucleotides, and small molecules.

Dietary Models

Dietary models are developed by manipulating the nutritional environment of genetically susceptible animals, such as providing a high-fat diet to SMN-deficient mice. This approach allows researchers to examine the influence of metabolic and environmental factors on SMA pathology and progression. The primary advantage is the capacity to study gene-environment interactions and assess the impact of dietary interventions on disease severity. Dietary models are valuable for evaluating adjunctive therapies, metabolic modulators, and personalized medicine strategies.

Invertebrate Models

Invertebrate models, including Drosophila melanogaster (fruit fly) and Danio rerio (zebrafish), are engineered to carry mutations or knockouts in orthologous SMA genes (e.g., smn1 in zebrafish, Khc in fruit flies). These models are generated using genetic crossing, mutagenesis, or CRISPR-based techniques. Their advantages include rapid generation times, cost-effectiveness, and suitability for large-scale genetic and drug screening. Invertebrate models are particularly useful for high-throughput phenotypic screening, target validation, and early-stage therapeutic discovery.

Protheragen delivers a full-spectrum SMA animal model development service, encompassing model selection, custom genetic engineering, colony management, phenotypic validation, and in vivo efficacy testing. We offer a range of key efficacy endpoints, including motor function assays (rotarod, grip strength), survival analysis, histopathological evaluation (motor neuron counts, muscle atrophy), molecular biomarker quantification (SMN protein levels, gene expression), and behavioral assessments. Our analytical capabilities extend to advanced imaging, next-generation sequencing, and biostatistical analysis. Rigorous quality control is maintained through genotyping, phenotypic scoring, and standardized protocols to ensure data reliability and reproducibility.

By partnering with Protheragen, you gain access to a scientifically rigorous, customizable, and end-to-end solution for SMA animal model development and therapeutic evaluation. Our expertise accelerates your research timeline, reduces risk, and enhances the translational potential of your SMA program. Contact us today to discuss your project needs and discover how Protheragen can advance your SMA research objectives.