Lith1 QTL Detail

Summary

• Symbol
  Lith1
• Name
  lithogenic gene 1

• Feature Type
  QTL
• IDs
  MGI:102584
  NCBI Gene: 109709
• Candidate Genes
  2 Genes

Location &
Maps

• Sequence Map
  Chr2:45347635-145312647 bp

  From MGI annotation of GRCm39
  

• View this region in JBrowse
  

• Genome Browsers
  Ensembl | UCSC | NCBI

• Genetic Map
  Chromosome 2, 47.93 cM (cM position of peak correlated region/marker)
• QTL Archive
  Wittenburg1 download
• Mapping Data
  9 experiments

Mutations,
Alleles, and
Phenotypes

• Phenotype Summary
  1 phenotype from 2 alleles in 1 genetic background
  1 phenotype reference
  

• All Mutations and Alleles
  2
• QTL
  2
• Find Mice (IMSR)
  1 strains or lines available

Sequences &
Gene Models

• NCBI Gene
  109709

Other
Accession IDs

MGD-MRK-19470

References

• Summaries
  All 17

  Phenotypes 1
• Earliest
  J:28288 Khanuja B, et al., Lith1, a major gene affecting cholesterol gallstone formation among inbred strains of mice. Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7729-33
• Latest
  J:104062 Henkel A, et al., Mice overexpressing hepatic Abcb11 rapidly develop cholesterol gallstones. Mamm Genome. 2005 Dec;16(12):903-8

Candidate Genes for Lith1:

Gene	Genome Location (GRCm39)	Reference	QTL Note
Abcb11	Chr2:69068626-69172958 (-)	J:88544	Abcb11, a candidate gene for Lith1 on mouse Chromosome 2, was examined in this study. Sequencing of Abcb11 failed to detect polymorphisms in the gene coding region between gallstone susceptible strain C57L/J and gallstone resistant strain AKR/J. Northernand Western blot analysis detected 3-fold increased mRNA and protein expression in C57L/J compared to AKR/J. However, Abcb11 transport function was decreased 9-fold in C57L/J compared to AKR/J. In addition, Abcb11-null mice display lithogenic bile. These results support the candidacy of Abcb11 as a candidate gene for Lith1.
Abcb11	Chr2:69068626-69172958 (-)	J:104062	Lith1 is a previously identified gallstone susceptibility QTL mapping to 41 cM on mouse Chromosome 2. Abcb11 at 38.4 cM colocalizes with Lith1 and is overexpressed in the gallstone-susceptible inbred strain C57/L compared to the gallstone-resistant inbred strain AKR/J. Authors evaluated animals carrying the Tg(RP23-291P1)1Flp transgene on an FVB/NJ genetic background to determine if Abcb11 overexpression accelerates gallstone formation. Male transgenic and FVB/NJ control animals were fed a lithogenic diet for up to 7 days. On the CHOW diet, Tg(RP23-291P1)1Flp transgenic animals and FVB/NJ controls did not develop cholesterol crsytals or gallstones. However, gallbladder bile from transgenic animals was significantly more hydrophobic compared to FVB/NJwild type controls. On day 4 of the lithogenic diet, 100% of transgenic animals exhibited bile cholesterol crystals and 25% had gallstones compared to 43% and 0%, respectively, of FVB/NJ controls. On day 7 of the lithogenic diet, 80% of transgenic animals had gallstones compared to 41% of FVB/NJ controls. These results support the hypothesis that overexpression of Abcb11 is responsible for the gallstone-susceptible effect of Lith1.
Nfe2l2	Chr2:75505857-75534985 (-)	J:88844	Authors indicate that Nfe212 may be the causitive gene for the Lith1 QTL. However other genes within the QTL region may also effect the Lith1 phenotype.