B6-hIGHMBP2 Mouse

The IGHMBP2 (Immunoglobulin mu binding protein 2) gene encodes an ATP-dependent helicase that is expressed throughout the body and contains a helicase structural domain, a single-stranded nucleic acid binding domain, and one zinc finger motif. It is involved in the regulation of DNA replication, mRNA splicing, transcription, and translation. Mutations in IGHMBP2 can lead to two different types of diseases: spinal muscular atrophy with respiratory distress type 1 (SMARD1) and Charcot-Marie-Tooth disease type 2S (CMT2S).

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a rare autosomal recessive motor neuron disease, with its main clinical symptom being diaphragmatic paralysis leading to respiratory distress, occurring mostly in infants aged 6 to 12 months. In addition, SMARD1 can also cause severe muscle atrophy that progresses from the distal to the proximal limbs, intrauterine growth retardation, weak crying, and sensory and autonomic nervous system defects ^[1]. Restrictive cardiomyopathy may be one of the phenotypes of SMARD1 ^[2]. Charcot-Marie-Tooth disease type 2S (CMT2S) is a rare hereditary neurological disease and is a subtype of Charcot-Marie-Tooth disease type 2 (CMT2). CMT2 is a group of hereditary peripheral neuropathies characterized by abnormal fibers or axons extending from the nerve cell body to muscles or sensory organs, reducing the strength of nerve impulses. The clinical characteristics of CMT2S include symmetrical distal limb weakness and muscle atrophy, with severe peripheral nerve damage.

Currently, ASO drugs and AAV-based gene therapy have emerged in the IGHMBP2-targeted drug pipeline for the treatment of SMARD1 and CMT2. Gene therapy is expected to become one of the most promising treatments for these diseases. However, since most ASO, AAV-based gene therapy, etc., act on the human IGHMBP2 gene, considering the differences between animals and humans in genes, humanizing the mouse gene will help promote the further clinical translation of therapies targeting IGHMBP2. This strain is a mouse Ighmbp2 gene humanized model and can be used for research on SMARD1 and CMT2S. The homozygous B6-hIGHMBP2 mice are viable and fertile. In addition, based on the independently developed TurboKnockout fusion BAC recombination technology, Cyagen can also generate hot mutation models based on this strain and provide customized services for specific mutations to meet the experimental needs in pharmacology and other fields related to SMARD1 and CMT2S.