B6;129S6-Fgl1^tm1Cuko/J

Stock number: 024004
Research areas: Cardiovascular Research, Developmental Biology Research, Diabetes and Obesity Research, Endocrine Deficiency Research, Internal/Organ Research

Description

Fgl1^-/- mice may be useful for studying metabolism and liver regeneration.

Detailed description

The transcription initiation codon and the secretory signal recognition peptide sequence, of the fibrinogen-like protein 1 (Fgl1) gene have been replaced with a loxP-flanked neomycin resistance (neo) cassette, abolishing gene expression. FGL1 is expressed in the liver and is involved in hepatocyte proliferation and repair. It has been found overexpressed in hepatocellular carcinomas and following acute liver injury. Homozygotes are viable and fertile. Fgl1^-/- mice are 37% heavier than wild type mice at three weeks of age. They are also longer and contain more adipose tissue. These mice have decreased plasma cholesterol, free fatty acid levels, and fasting hyperglycemia with enhanced gluconeogenesis. Adipose tissue morphology is abnormal in Fgl1^-/- mice. Brown adipose tissue contains larger lipid droplets and has reduced number of nuclei, while white adipocytes are larger and fewer in number than in wildtype mice.

Development

A targeting vector was designed to replace exons 2-3, including the transcription initiation codon, of the fibrinogen-like protein 1 (Fgl1) gene with a loxP-flanked neomycin resistance (neo) cassette. The construct was electroporated into (129S6/SvEvTac x C57BL/6J)F1-derived PTL1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric males were bred to C57BL/6 females. Fgl1^-/- mice were maintained on a mixed background. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Fgl1^tm1Cuko
Name: targeted mutation 1, Chinweike Ukomadu
MGI accession ID: MGI:5510996
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Fgl1
Marker name: fibrinogen-like protein 1
Marker synonyms: Frep1; HFREP1; HP-041; HPS; LFIRE1; LFIRE-1; MGC:37822
Chromosome: 8
Strain of origin: (129S6/SvEvTac x C57BL/6J)F1
Molecular note: A floxed neomycin resistance cassette replaced exons 2 and 3. Western blot analysis confirmed the absence of protein in the liver.