Testing the Ret and Sema3d genetic interaction in mouse enteric nervous system development

Ashish Kapoor, Dallas R. Auer, Dongwon Lee, Sumantra Chatterjee, Aravinda Chakravarti

Research output: Contribution to journalArticle

Abstract

For most multigenic disorders, clinical manifestation (penetrance) and presentation (expressivity) are likely to be an outcome of genetic interaction between multiple susceptibility genes. Here, using gene knockouts in mice, we evaluated genetic interaction between loss of Ret and loss of Sema3d, two Hirschsprung disease susceptibility genes. We intercrossed Ret and Sema3d double null heterozygotes to generate mice with the nine possible genotypes and assessed survival by counting various genotypes, myenteric plexus presence by acetylcholinesterase staining and embryonic day 12.5 (E12.5) intestine transcriptome by RNA-sequencing. Survival rates of Ret wild-type, null heterozygote and null homozygote mice at E12.5, birth and weaning were not influenced by the genotypes at Sema3d locus and vice versa. Loss of myenteric plexus was observed only in all Ret null homozygotes, irrespective of the genotypes at Sema3d locus, and Sema3d null heterozygote and homozygote mice had normal intestinal innervation. As compared with wild-type mice intestinal gene expression, loss of Ret in null homozygotes led to differential expression of 300 genes, whereas loss of Sema3d in null homozygotes had no major consequence and there was no evidence supporting major interaction between the two genes influencing intestine transcriptome. Overall, given the null alleles and phenotypic assays used, we did not find evidence for genetic interaction between Ret and Sema3d affecting survival, presence of myenteric plexus or intestine transcriptome.

Original languageEnglish (US)
Pages (from-to)1811-1820
Number of pages10
JournalHuman Molecular Genetics
Volume26
Issue number10
DOIs
StatePublished - May 15 2017

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Enteric Nervous System
Homozygote
Myenteric Plexus
Heterozygote
Genotype
Transcriptome
Intestines
Genes
RNA Sequence Analysis
Gene Expression
Hirschsprung Disease
Gene Knockout Techniques
Penetrance
Disease Susceptibility
Acetylcholinesterase
Weaning
Knockout Mice
Alleles
Parturition
Staining and Labeling

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Kapoor, A., Auer, D. R., Lee, D., Chatterjee, S., & Chakravarti, A. (2017). Testing the Ret and Sema3d genetic interaction in mouse enteric nervous system development. Human Molecular Genetics, 26(10), 1811-1820. https://doi.org/10.1093/hmg/ddx084

Testing the Ret and Sema3d genetic interaction in mouse enteric nervous system development. / Kapoor, Ashish; Auer, Dallas R.; Lee, Dongwon; Chatterjee, Sumantra; Chakravarti, Aravinda.

In: Human Molecular Genetics, Vol. 26, No. 10, 15.05.2017, p. 1811-1820.

Research output: Contribution to journalArticle

Kapoor, A, Auer, DR, Lee, D, Chatterjee, S & Chakravarti, A 2017, 'Testing the Ret and Sema3d genetic interaction in mouse enteric nervous system development', Human Molecular Genetics, vol. 26, no. 10, pp. 1811-1820. https://doi.org/10.1093/hmg/ddx084
Kapoor, Ashish ; Auer, Dallas R. ; Lee, Dongwon ; Chatterjee, Sumantra ; Chakravarti, Aravinda. / Testing the Ret and Sema3d genetic interaction in mouse enteric nervous system development. In: Human Molecular Genetics. 2017 ; Vol. 26, No. 10. pp. 1811-1820.
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