C57BL/6J-Lta^hlb382/J

Stock number: 005579
Strain synonyms: HLB-382, HLB382
Research areas: Hematological Research

Description

These mice carry an ENU-induced mutation resulting in an increased white blood cell count.

Detailed description

Mice that are homozygous for the mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Screening of third generation mice (G3)identified a non-fasted female (born 10/9/2003) with an increased white blood cell count of 15.39 x 103 cells/ul, which is approximately 92% higher than controls. This mutant mouse strain may be useful in studies of leukocytosis.

Development

Following multidose ethylnitrosourea (ENU) treatments to induce mutations in male founder C57BL/6J mice (Stock No. 000664), a forward genetic screen was utilized to identify phenotypic deviants in complex heart, lung, blood, and sleep disorders, at the Mouse Heart, Lung, Blood, and Sleep Disorders (HLBS) Center at The Jackson Laboratory. The phenotype was mapped to chromosome 17. Sequencing of the candidate gene Lta, lymphotoxin A, revealed an insertion of a cytosine occurred between nucleotides 16 and 17 of the second exon. This is predicted to cause a frameshift mutation from amino acid 6 and translation of a theoretical new peptide of 173 amino acids with a premature stop codon in exon 4. Heterozygotes were crossed to generate homozygotes. The mice have been maintained on a C57BL/6J background.

Allele

Symbol: Lta^hlb382
Name: heart, lung and blood 382
MGI accession ID: MGI:3575123
Generation method: Chemically induced (ENU)
Marker symbol: Lta
Marker name: lymphotoxin A
Marker synonyms: hlb382; LT; LT[a]; LT-[a]; LTalpha; LT-alpha; Ltx; lymphotoxin; lymphotoxin alpha; TNF beta; Tnfb; TNF-beta; TNFSF1; Tnfsf1b; TNLG1E
Chromosome: 17
Strain of origin: C57BL/6J
Molecular note: This phenotypic mutant was identified in an ENU mutagenesis screen. An insertion of a cytosine occurred between nucleotides 16 and 17 of the second exon. This is predicted to cause a frameshift mutation from amino acid 6 and translation of a theoretical new peptide of 173 amino acids with a premature stop codon in exon 4. Because Ltb and Tnf are found in nearby genomic locations, their sequence and expression were analyzed and found to be normal. Intra-cell flow cytometry failed to detect any Lta expression in activated B-cells.