B6N.129-Acsbg1^tm1Mld/J

Stock number: 024754
Product name: GR-LACS/lipidosin null
Research areas: Cell Biology Research, Metabolism Research, Reproductive Biology Research

Description

GR-LACS^-/- mice have a neo cassette replacing exons 1-2 and part of exon 2 of the Acsbg1 gene, abolishing gene expression in the testis, ovary, adrenal gland, and brain. These mice may be useful for studying the mechanisms of gonadotropin-induced desensitization of testosterone production.

Detailed description

In this strain, a neo cassette replaces exons 1-2 of the acyl-CoA synthetase bubblegum family member 1 (Acsbg1) gene, abolishing gene expression. ACSBG1, also known as gonadotropin-regulated long chain acyl-CoA synthetase (GR-LACS) or lipidosin, is an enzyme that is transcriptionally regulated by gonadotropin in rat testis. GR-LACS is involved in protein and lipid transport, enzyme activation, protein acylation, cell signaling and transcription, and plays a role in brain very long-chain fatty acids (VLCFA) metabolism and myelinogenesis. GR-LACS has also been associated with X-linked adrenoleukodystrophy (X-ALD), an adreno/neurodegenerative disorder with accumulation of VLCFA in tissues and plasma. Homozygous GR-LACS^-/- mice are viable and fertile. Mice have increased levels of long chain fatty acid in testis, ovary, brain, and decreased adrenal gland palmitic, oleic, and linoleic acid levels. Males exhibit nuclear inclusions in Leydig cells and increased gonadotropin induced changes in testosterone production. These mice have no apparent phenotypic abnormalities associated with X-ALD.

Development

A targeting vector was designed in the laboratory of Dr. Maria L Dufau (Molecular Endocrinology NICHD, NIH) to replace exons 1-2 of the acyl-CoA synthetase bubblegum family member 1 (Acsbg1) gene with a neomycin resistance (neo) cassette. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl⁺ -derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric males were bred to C57BL/6N to generate a colony of GR-LACS^-/- mice. These mice were bred to C57BL/6N mice for at least 15 generations. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6NJ (Stock No. 005304) for at least one generation to establish the colony.

Allele

Symbol: Acsbg1^tm1Mld
Name: targeted mutation 1, Maria L Dufau
MGI accession ID: MGI:3851593
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Acsbg1
Marker name: acyl-CoA synthetase bubblegum family member 1
Chromosome: 9
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: A genomic fragment including exons 1 and 2 was replaced with a neo cassette via homologous recombination. Northern blot analysis confirmed the absence of RNA expression in testis from homozygous mice. Western blot analysis confirmed the absence of protein expression in the testis, ovary, adrenal gland, and brain from homozygous mice.