Atypical Auditory Brainstem Response and Protein Expression Aberrations Related to ASD and Hearing Loss in the Adnp Haploinsufficient Mouse Brain

Neurochem Res. 2019 Jun;44(6):1494-1507. doi: 10.1007/s11064-019-02723-6. Epub 2019 Jan 18.

Abstract

Autism is a wide spread neurodevelopmental disorder with growing morbidity rates, affecting more boys than girls worldwide. Activity-dependent neuroprotective protein (ADNP) was recently recognized as a leading gene accounted for 0.17% of autism spectrum disorder (ASD) cases globally. Respectively, mutations in the human ADNP gene (ADNP syndrome), cause multi-system body dysfunctions with apparent ASD-related traits, commencing as early as childhood. The Adnp haploinsufficient (Adnp+/-) mouse model was researched before in relations to Alzheimer's disease and autism. Adnp+/- mice suffer from deficient social memory, vocal and motor impediments, irregular tooth eruption and short stature, all of which corresponds with reported phenotypes in patients with the ADNP syndrome. Recently, a more elaborated description of the ADNP syndrome was published, presenting impediments such as hearing disabilities in > 10% of the studied children. Irregular auditory brainstem response (ABR) has been connected to ASD-related cases and has been suggested as a potential hallmark for autism, allowing diagnosis of ASD risk and early intervention. Herein, we present detriment hearing in the Adnp+/- mice with atypical ABR and significant protein expression irregularities that coincides with ASD and hearing loss studies in the brain.

Keywords: ADNP syndrome; Activity-dependent neuroprotective protein ADNP; Adnp haploinsufficient Adnp +/−; Auditory brainstem response ABR; Developmental delays; Hearing loss.

MeSH terms

  • Animals
  • Auditory Cortex
  • Autism Spectrum Disorder / complications*
  • Autism Spectrum Disorder / genetics
  • Choline O-Acetyltransferase / metabolism
  • Disease Models, Animal*
  • Evoked Potentials, Auditory, Brain Stem / genetics*
  • Female
  • Glutamate Decarboxylase / metabolism
  • Hair Cells, Auditory / cytology
  • Hearing Loss / etiology*
  • Hearing Loss / genetics
  • Homeodomain Proteins / genetics*
  • Male
  • Mice
  • Mutation
  • Nerve Tissue Proteins / genetics*

Substances

  • Adnp protein, mouse
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Choline O-Acetyltransferase
  • Glutamate Decarboxylase
  • glutamate decarboxylase 1