This CRISPR/Cas9 generated mutant of the Adnp (activity-dependent neuroprotective protein) gene carries a 14 nucleotide deletion in exon 5. Mice heterozygous for the allele exhibit learning deficits and maybe useful for the study of Helsmoortel-Van der Aa syndrome.
Frank Kooy, University of Antwerp
CRISPR/Cas9 endonuclease mediated genome editing of the Adnp (activity-dependent neuroprotective protein) gene introduced a 14 nucleotide deletion in exon 5. The targeted Adnp gene encodes a putative transcription factor that is involved in chromatin remodelling. Mutations in Adnp are associated with Helsmoortel-Van der Aa syndrome, a condition characterized by learning disabilities and autism spectrum disorder. Mice heterozygous for the mutation are viable and fertile. However, the donating investigator reports that heterozygote x wild type matings produce less than the expected 50% of pups carrying the mutant allele. In addition, heterozygote x heterozygote matings have not produced pups under standard breeding conditions. Mice heterozygous for the allele exhibit learning deficits as demonstrated in the in the Morris water maze test as well as increased anxiety and repetitive behavior. This strain maybe useful for the study of Helsmoortel-Van der Aa syndrome, autism and learning deficits in general and specific types of chromatin remodeling.
This model is made available by Frank Kooy (University of Antwerp) with support from the Simons Foundation Autism Research Initiative (SFARI).
CRISPR/Cas9 genome editing introduced 14 nucleotide deletion such that Leucine822 is replaced by Histidine and is followed by 4 amino acids (ERIK) and a termination codon in exon 5 of the Adnp gene. Single guide RNA and Cas9 endonuclease were introduced into the cytoplasm of C57BL/6NJcl-derived fertilized eggs with well recognized pronuclei. The deletion causes a frameshift and is predicted to result in a truncated protein. Correctly targeted embryos were transferred to pseudopregnant females. Correctly targeted pups were identified by sequencing and PCR and further bred to C57BL/6NCrl to maintain the colony by the donating lab (see SNP note below). Upon arrival. mice were bred to C57BL/6NJ (Stock No. 005304) for at least one generation to establish the colony.
A 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. All 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6J genetic background.
|Allele Name||endonuclease-mediated mutation 1, Frank Kooy|
|Allele Type||Endonuclease-mediated (Null/Knockout)|
|Gene Symbol and Name||Adnp, activity-dependent neuroprotective protein|
|Strain of Origin||C57BL/6NJcl|
|Molecular Note||CRISPR/Cas9 genome editing introduced a 14 nucleotide deletion such that Leucine822 is replaced by Histidine and followed by 6 amino acids and a termination codon in exon 5. The deletion causes a frameshift and is predicted to result in a truncated protein.|
When maintaining a live colony, heterozygote mice may be bred to wild type from the colony or C57BL/6NJ mice (Stock No. 005304). Heterozygous x heterozygote matings are non-productive. Heterozygote x wild type matings produce less than the expected number of pups carrying the mutant allele.
When using the C57BL/6-Adnpem1Ant/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #033128 in your Materials and Methods section.