Rolling Nagoya mouse strain (PROD-rol/rol) with classic piebald mutation

Area of Science:

• Genetics
• Neuroscience
• Animal Models

Background:

• Ataxic rolling Nagoya (PROD-rol/rol) mice possess a mutation in the Cacna1a gene, affecting the Cav2.1 channel.
• These mice also exhibit piebald spotting, suggesting a mutation in the piebald spotting (s) locus.

Purpose of the Study:

• To investigate the endothelin receptor type B (Ednrb) gene in PROD-rol/rol mice.
• To compare gene expression patterns of Ednrb and Cacna1a between PROD-rol/rol, PROD-s/s, and C57BL/6J mice.

Main Methods:

• Genomic and mRNA sequence analysis of the Ednrb gene.
• Polymerase chain reaction (PCR) for mutation detection.
• Gene expression analysis in the colon.
• Microsatellite genotyping for genetic origin determination.

Main Results:

• Identified two silent nucleotide substitutions and a retroposon insertion in intron 1 of the Ednrb gene in PROD-rol/rol mice.
• Ednrb and Cacna1a expression levels were diminished in PROD mice compared to C57BL/6J mice.
• PROD strain chromosome 14 regions are derived from Japanese fancy piebald mice.

Conclusions:

• PROD-rol/rol mice possess mutations in both Ednrb and Cacna1a genes.
• The absence of an intact Ednrb gene in the PROD strain necessitates the use of congenic rolling mice for studying Cav2.1 channel dysfunction.