Abstract
Synaptosomal-associated protein 29 (SNAP29) encodes a member of the SNARE family of proteins implicated in numerous intracellular protein trafficking pathways. SNAP29 maps to the 22q11.2 region and is deleted in 90% of patients with 22q11.2 deletion syndrome (22q11.2DS). Moreover, bi-allelic SNAP29 mutations in patients are responsible for CEDNIK (cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma) syndrome. A mouse model that recapitulates abnormalities found in these syndromes is essential for uncovering the cellular basis of these disorders. In this study, we report that mice with a loss of function mutation of Snap29 on a mixed CD1;FvB genetic background recapitulate skin abnormalities associated with CEDNIK, and also phenocopy neurological and ophthalmological abnormalities found in CEDNIK and a subset of 22q11.2DS patients. Our work also reveals an unanticipated requirement for Snap29 in male fertility and supports contribution of hemizygosity for SNAP29 to the phenotypic spectrum of abnormalities found in 22q11.2DS patients.
Highlights
Synaptosomal-associated protein 29 (SNAP29) encodes a member of the SNARE family of proteins implicated in numerous intracellular protein trafficking pathways
We show that mice with constitutive loss of function mutation in Snap[29] on this mixed genetic background survive and exhibit: skin abnormalities, neurological defects, facial dysmorphism, psychomotor retardation, and fertility problems with variable expressivity and incomplete penetrance
It is recommended that genetically engineered mouse models be analyzed on multiple genetic backgrounds, so as to identify any major roles played by differences in genetic backgrounds[15]
Summary
Synaptosomal-associated protein 29 (SNAP29) encodes a member of the SNARE family of proteins implicated in numerous intracellular protein trafficking pathways. We report that mice with a loss of function mutation of Snap[29] on a mixed CD1;FvB genetic background recapitulate skin abnormalities associated with CEDNIK, and phenocopy neurological and ophthalmological abnormalities found in CEDNIK and a subset of 22q11.2DS patients. 22q11.2DS patients have heterogeneous clinical presentations associated with multi-organ dysfunction including cardiac and palate abnormalities, hypoparathyroidism, neurological and motor defects, epilepsy, cognitive deficits, and neuropsychiatric illness (e.g., schizophrenia) These dysfunctions show incomplete penetrance and variable expressivity depending on the patient’s age[1]. We show that mice with constitutive loss of function mutation in Snap[29] on this mixed genetic background survive and exhibit: skin abnormalities, neurological defects, facial dysmorphism, psychomotor retardation, and fertility problems with variable expressivity and incomplete penetrance. This mouse model can be used to uncover the etiology of abnormalities found in patients with mutations of SNAP29
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
