SAMN54266182
External Id
University of Arkansas for Medical Sciences
INSDC center name
2025-12-22T00:00:00Z
INSDC first public
2025-12-22T15:01:20.627Z
INSDC last update
live
INSDC status
Model organism or animal
NCBI submission model
Model.organism.animal.1.0
NCBI submission package
Adult
age
2020-06-01
collection_date
Background: Transgenic mice which harbor a lacZ reporter gene typically do not display an overt phenotype. However, when generating mice that use the mouse Plp1 promoter to drive expression of lacZ, one of the founders had a mutant phenotype, most notably, low body size. Line 781 was established with this founder. The mutant phenotype is 100% penetrant with the transgene. Hence, the purpose of this study was to identify the genomic rearrangements in mutant animals from Line 781 and to perform a longitudinal growth study, in hopes of identifying novel causes of low body size. Results: Fluorescence in situ hybridization (FISH) analysis revealed that the transgene in Line 781 integrated in chromosome 2. Moreover, this chromosome (der2) had a reciprocal translocation with chromosome 1. The longitudinal growth study for Line 781 demonstrated that the mutant (transgenic) mice were smaller than their wild-type (nontransgenic) counterparts throughout postnatal life. Optical genome mapping established that the reciprocal translocation is unbalanced with deletion of approximately 3.9 (chr1) and 1.8 (chr2) Mbp from the rearranged (derivative) chromosomes, thus resulting in a monosomy over these regions in the mutant genome. Optical genome mapping also determined that five complete copies of the transgene lay directly between the translocation junction of der2. Sanger sequencing of PCR products that cross a junction were used to determine the chromosomal breakpoints and transgene integration site, precisely. In all, the complex chromosomal rearrangements in Line 781 span 38 protein-coding genes that result in the transection of 1 gene from chr1 and deletion of 33 and 4 genes from chr1 and chr2, respectively. Conclusions: An unbalanced reciprocal translocation marked by a transgene gives rise to a low body size phenotype in mouse. Thirty-eight protein-coding genes are either partially or fully deleted from the rearranged chromosomes (der1 and der2), resulting in a monosomy over these regions in the mutant genome. Hence, it is possible that haploinsufficiency of one or more of the gene products is the underlying etiology in mutant animals. Moreover, Line 781 can serve as an animal model of 1q24 deletion syndrome in human patients with interstitial deletion of the syntenic region.
description
USA: Little Rock, Arkansas
geo_loc_name
Mus musculus
http://purl.obolibrary.org/obo/NCBITaxon_10090
organism
Mutant
phenotype
female
sex
C57BL/6
strain
Liver
tissue
Model organism or animal sample from Mus musculus
title