C57BL/6J-Lrrc58^em3Dpbl/J

Stock number: 041175
Product name: Lrrc58{-134}, Lrrc58^-134
Research areas: Cell Biology Research, Developmental Biology Research

Description

Lrrc58{-134} mice carry a 134-nt deletion encompassing the 3' UTR site of the mouse Lrrc58 (leucine rich repeat containing 58) gene required for target-directed degradation of miR-503-5p.

Detailed description

Lrrc58{-134} mice carry a 134-nt deletion encompassing the 3' UTR site of the mouse Lrrc58 (leucine rich repeat containing 58) gene required for target-directed degradation of miR-503-5p.

The Lrrc58{TDMD_mut} (Stock No. 041173), Lrrc58{-402} (Stock No. 041174), and Lrrc58{-134} (Stock No. 041175) mutations are predicted to cause the same molecular disruption, and experimental results are consistent between the alleles. The Lrrc58{TDMD_mut} allele carries seven nucleotide substitutions in the miR-503 complementary site, which specifically impairs its ability to trigger microRNA degradation. The Lrrc58{-134} and Lrrc58{-402} alleles have the miR-503 complementary site disrupted, but in the context of larger genomic deletions. The donating laboratory treats the three alleles as interchangeable.

Homozygous Lrrc58 mutant mice produce elevated levels of miR-503-5p in the embryonic day 18.5 (E18.5 heart and lung) due to impaired target-directed microRNA degradation (TDMD) and are 4.8% smaller than wildtype littermates at E18.5. This body size phenotype persists into adulthood; 8-week-old mice are approximately 7–8% smaller than wildtype littermates. Heterozygotes also show an elevation of miR-503-5p levels, but to a lesser degree.

Bulk mRNA sequencing of embryonic day 18.5 (E18.5) heart showed an ~12% increase in Lrrc58 mRNA in mutant mice, with no statistically significant difference between mutant and wildtype samples. Protein levels were not assessed.

Development

CRISPR-Cas9 methodology was used to create a 134-nt deletion encompassing the 3' UTR site of the mouse Lrrc58 gene on mouse Chromosome 16 (ENSMUST00000078717.7). The mutation was created in C57BL/6J embryos. Resultant mice were maintained on a C57BL/6J background by the donating laboratory. Upon arrival, sperm was cryopreserved. To establish a live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Allele

Symbol: Lrrc58^em3Dpbl
Name: endonuclease-mediated mutation 3, David P Bartel
MGI accession ID: MGI:8246768
Generation method: Endonuclease-mediated
Attributes: Modified regulatory region
Synonyms: Lrrc58{-134}
Marker symbol: Lrrc58
Marker name: leucine rich repeat containing 58
Marker synonyms: 1810012N18Rik; C330018J07Rik; RGD1307440
Chromosome: 16
Strain of origin: C57BL/6J
Molecular note: CRISPR-Cas9 methodology was used to create a 134 bp deletion in a 3' UTR site of the mouse Lrrc58 gene. The mutant allele contains a 134nt deletion that abrogates the transcript's ability to mediate target-directed microRNA degradation of miR-503.