Snap29 mutant mice recapitulate neurological and ophthalmological abnormalities associated with 22q11 and CEDNIK syndrome

Commun Biol. 2019 Oct 11:2:375. doi: 10.1038/s42003-019-0601-5. eCollection 2019.

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.

Keywords: Disease model; Infertility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DiGeorge Syndrome / genetics*
  • DiGeorge Syndrome / pathology
  • DiGeorge Syndrome / physiopathology
  • Disease Models, Animal
  • Eye Abnormalities / genetics
  • Eye Abnormalities / pathology
  • Female
  • Gene Expression Regulation, Developmental
  • Hemizygote
  • Humans
  • Infertility, Male / genetics
  • Infertility, Male / pathology
  • Keratoderma, Palmoplantar / genetics*
  • Keratoderma, Palmoplantar / pathology
  • Keratoderma, Palmoplantar / physiopathology
  • Loss of Function Mutation
  • Male
  • Mice
  • Mice, Knockout
  • Mice, Mutant Strains
  • Nervous System Malformations / genetics
  • Nervous System Malformations / pathology
  • Neurocutaneous Syndromes / genetics*
  • Neurocutaneous Syndromes / pathology
  • Neurocutaneous Syndromes / physiopathology
  • Phenotype
  • Pregnancy
  • Qb-SNARE Proteins / deficiency*
  • Qb-SNARE Proteins / genetics*
  • Qc-SNARE Proteins / deficiency*
  • Qc-SNARE Proteins / genetics*

Substances

  • Qb-SNARE Proteins
  • Qc-SNARE Proteins
  • Snap29 protein, mouse

Supplementary concepts

  • Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome

Grants and funding