Functional Polymorphisms of the Lss and Fdft1 Genes in Laboratory Rats

• MORI Masayuki

  Department of Aging Biology, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine

• SAWASHITA Jinko

  Department of Aging Biology, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine

• HIGUCHI Keiichi

  Department of Aging Biology, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine

Abstract

We previously identified mutant alleles of the lanosterol synthase (Lss) and farnesyl diphosphate farnesyl transferase 1 (Fdft1) genes, which function in the cholesterol biosynthesis pathway, as determinants for hereditary cataracts in the SCR rat strain. Lss^S and Fdft1^S were established as hypomorphic alleles with missense nucleotide substitutions, while Lss^l is a null allele with nucleotide deletion/insertion mutations. Here we report a more detailed characterization of the rat Lss and Fdft1 genes. Screening of various laboratory rat strains revealed that the hypomorphic Lss^S and Fdft1^S alleles are not specific to the SCR strain, but are widely prevalent in other laboratory rat strains. Meanwhile, Lss^l was not found in any rat strains examined. It was also found that functional inter-strain polymorphisms are present in the Lss upstream regulatory region. The BN strain had a higher potential for expression of Lss transcripts than ACI and SCR under conditions where cholesterol synthesis is necessary. SCR was less efficient than BN and ACI in suppressing Lss transcription in circumstances when cholesterol synthesis should be halted. These findings not only imply that there is a genetic polymorphism for cholesterol homeostasis in laboratory rats, but also point to the possibility that rat strains with different Lss alleles exhibit different responses to measures intervening in cholesterol metabolism.<br>

Journal

• Experimental Animals

  Experimental Animals 56 (2), 93-101, 2007

  Japanese Association for Laboratory Animal Science

Keywords

• farnesyl diphosphate farnesyl transferase 1
• laboratory rat
• lanosterol synthase
• polymorphism

Details

• CRID: 1390001205046910720
• NII Article ID: 130000068039
• NII Book ID: AA11032321
• DOI: 10.1538/expanim.56.93
• ISSN: 18817122
• ISSN: 00075124
• ISSN: 13411357
• NDL BIB ID: 8704343
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I8704343
• Web Site: http://www.jstage.jst.go.jp/article/expanim/56/2/56_2_93/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2007266373
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
• Abstract License Flag: Disallowed