RRC ID 77784
Author Miyasaka Y, Kobayashi T, Gotoh N, Kuga M, Kobayashi M, Horio F, Hashimoto K, Kawabe T, Ohno T.
Title Neonatal lethality of mouse A/J-7SM consomic strain is caused by an insertion mutation in the Dchs1 gene.
Journal Mamm Genome
Abstract Homosomic mice of the A/J-7SM consomic mouse strain that introduced the entire chromosome 7 (Chr 7) of SM/J into the A/J strain exhibited neonatal lethality. We tentatively maintained segregating inbred strains (A/J-7ASM and A/J-7DSM) in which the central portion of Chr 7 was heterozygous for the A/J and SM/J strains, and the centromeric and telomeric sides of Chr 7 were homozygous for the SM/J strain, instead of the A/J-7SM strain. Based on the chromosomal constitution of Chr 7 in A/J-7ASM and A/J-7DSM mice, the causative gene for neonatal lethality in homosomic mice was suggested to be located within an approximately 1.620 Mb region between D7Mit125 (104.879 Mb) and D7Mit355 (106.499 Mb) on Chr 7. RT-PCR analysis revealed that homosomic mice lacked dachsous cadherin-related 1 (Dchs1), which is located within the D7Mit125 to D7Mit355 region and functions in the regulation of planar cell polarity. Screening for mutations in Dchs1 indicated that homosomic mice possessed an early transposable (ETn)-like sequence in intron 1 of Dchs1. Moreover, an allelism test between Dchs1 ETn-like-insertion alleles detected in homosomic mice and CRISPR/Cas9-induced Dchs1 deletion alleles revealed that Dchs1 is a causative gene for neonatal lethality in homosomic mice. Based on these results, we concluded that in the A/J-7SM strain, ETn-like elements were inserted into intron 1 of SM/J-derived Dchs1 during strain development, which dramatically reduced Dchs1 expression, thus resulting in neonatal lethality in homosomic mice. Additionally, it was suggested that the timing of lethality in Dchs1 mutant mice is influenced by the genetic background.
Volume 34(1)
Pages 32-43
Published 2023-3-1
DOI 10.1007/s00335-022-09966-9
PII 10.1007/s00335-022-09966-9
PMID 36434174
MeSH Alleles Animals Cadherins* / genetics Cadherins* / metabolism Chromosomes* Mice Mutagenesis, Insertional Mutation
IF 2.287
Mice RBRC04698 RBRC04699