B6.129S(FVB)-Anxa4^{Gt(OST134786)Lex}/KaeJ

Stock number: 010532
Research areas: Cancer Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

Mice that are homozygous for this targeted mutation of Anxa4 (annexin A4) exhibit an impaired hepatic inflammatory response. This mutant mouse strain may be useful in studies of inflammation and liver cancer.

Detailed description

Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Homozygous pups on the C57BL/6 background are smaller than wildtype littermates. Homozygous males become infertile if abdominal fat accumulates. Cell-specific alternative splicing of the Anx A4 transcript can yield three distinct mRNAs (Anx A4a, b and c) that are differentially expressed yet produce protein of identical sequence. In these animals, only the widely distributed AnxA4a transcript is disrupted, eliminating protein translation from this splice form. An aberrant gene product, a fusion transcript of exon a and the neomyocin resistance gene, (mRNA) is detected by RT-PCR analysis. Expression of Anx A4b and A4c transcripts is unchanged. No gene product (protein) is detected in heart or lung, low levels are detected in kidney, liver, and testis, and high levels are in duodenum, jejunum, ileum, and colon by Western blot analysis. Homozygotes exhibit an impaired hepatic inflammatory response. This mutant mouse strain may be useful in studies of inflammation and liver cancer.

Development

A gene trap construct was electroporated into 129 derived embryonic stem (ES) cells and was found to be inserted into the first intron, downstream of exon a. Correctly targeted ES cells were injected into albino C57BL/6 blastocysts. The resulting male chimeric animals were crossed to albino C57BL/6 females. The mice were crossed to FVB/N and then backcrossed to C57BL/6 for 6 generations before being made homozygous. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J once to establish the colony.

Allele

Symbol: Anxa4^{Gt(OST134786)Lex}
Name: gene trap OST134786, Lexicon Genetics
MGI accession ID: MGI:3530283
Generation method: Gene trapped
Attributes: Hypomorph; Modified isoform(s)
Marker symbol: Anxa4
Marker name: annexin A4
Chromosome: 6
Strain of origin: 129S5/SvEvBrd
Molecular note: The gene locus produces three different transcript variants that express the same 35-kDa protein but differ in their upstream untranslated region (UTR). A gene trap inserted downstream of "exon a", a non-coding exon that lies 27 kb upstream from the first coding exon. This insertion disrupted the UTR for one transcript variant of the gene locus but left intact two other transcript variants. Homozygotes for this allele are hypomorphs with the only strong gene expression occurring in the intestinal tract while wild-type mice have strong gene expression in numerous tissues including heart, kidney, liver, lung, stomach, and the intestinal tract.