Method for constructing autistic model dogs

Abstract

The present invention relates to a method for preparing autistic model dogs by gene editing techniques, obtained autistic model dogs, and cells and tissues of the autistic model dogs. The method comprises the steps of: (1) acquiring Shank3 knockout type autistic model canine fertilized eggs by using a gene editing technique; and (2) transplanting the Shank3 knockout type autistic model canine fertilized eggs to one fallopian tube of a female dog subjected to egg flushing on bilateral fallopian tubes, thereby preparing the Shank3 knockout type autistic model dogs.

Description

technical field [0001] The invention relates to a method for establishing an autism disease model dog by gene editing technology, the obtained autism disease model dog, and cells and tissues of the autism model dog. Background technique [0002] Dogs are currently one of the most commonly used experimental animals in basic medical research and teaching, especially playing an important role in experimental research in physiology, pharmacology and pathophysiology. Through the whole genome sequencing analysis of dogs, a total of about 19,300 genes have been identified, of which about 18,000 genes are the same as known human genes, and the similarity between the genome and human is higher than that of other experimental animals such as mice. Dogs are also very similar to humans in terms of hereditary diseases. There are more than 360 genetic diseases such as cancer, heart disease, deafness, blindness and immune nervous system diseases that are the same as humans, and are suitabl...

AI Technical Summary

Problems solved by technology

So far, six types of molecular defects of the SHANK3 gene have been identified in more than 1000 ASD patients: 1. 22q13.3 deletion (5-10Mb) or ring chromosome 22 visible on cytogenetic testing; 2. Microdeletion (0.1-4Mb); 3. Small amplification; 4. Intragenic breakpoint translocation; 5. Small intragenic deletion (<100kb); and 6. Point mutation, etc.

Gene mutant mouse models are the mainstream way to study the pathogenesis of diseases related to human SHANK3 mutations. At present, 15 autistic mouse strains with different mutation types have been developed, but the phenotypes are very different, and some show abnormal social interaction. , abnormal communication and repetitive stereotyped behavior, but some symptoms are not obvious

At the same time, it is worth noting that from the results of mouse studies, most of them have phenotypes when they are homozygous mutations, and heterozygotes tend to be normal, which is significantly different from humans.

Recently, there are also reports on rat and monkey SHANK3 gene knock-out models. However, due to the long breeding cycle of monkeys, high cost, and relatively difficult phenotype detection, it is difficult to be widely used in disease model research.

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