Mice that are homozygous for this targeted mutation of Tmpo, thymopoietin, or Lap2α, have abnormal lamin localization, exhibit delayed contact-mediated cell cycle arrest, and increased epidermal, erythroid and epithelial progenitor cells numbers. This mutant mouse strain may be useful in studies of cell cycle regulation, epidermal proliferation and differentiation, and laminopathic diseases.
Roland Foisner, Medical University Vienna
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No LAP2α gene product (mRNA or protein) is detected by Northern or Western blot analysis of primary fibroblasts from neonates. Expression of other TMPO isoforms was not significantly affected. A-type lamin localization is abnormal with decreased lamin in the nucleoplasm. Primary fibroblasts isolated from homozygotes exhibit delayed contact-mediated cell cycle arrest and attain a 1.5 fold increased density before cell cycle arrest compared to wildtype. Homozygotes display thickened plantar paw epidermis due to a twofold increase in proliferating cells. Hematocrit levels are increased. Mutants have a fourfold increased number of erythroid progenitor cells in the spleen and a smaller increase in erythroid progenitor cells in bone marrow. Large intestine crypts are lengthened in mutant mice. The colon epithelium has 20% more actively proliferating epithelial cells when compared to wildtype controls.
A targeting vector containing an FRT site flanked PGKneo cassette and a diphtheria toxin cassette was used to insert loxP sites flanking exon 4. The construct was electroporated into 129S1/Sv-Oca2+ Tyr+ Kitl+ derived W9.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting heterozygotes were intercrossed to generate homozygotes, which were then crossed to a transgenic strain on a mixed genetic background that ubiquitously expresses Cre recombinase. Mice that had successfully undergone Cre recombination and no longer contained exon 4 or the PGKneo cassette were backcrossed to C57BL/6 for 12 generations to remove the Cre transgene. A male mouse was then crossed to a female B6129F1 mouse. Upon arrival at The Jackson Laboratory the mice were crossed to C57BL/6J once to establish the colony.
|Allele Name||targeted mutation 1.1, Roland Foisner|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Tmpo, thymopoietin|
|Gene Synonym(s)||5630400D24Rik; 5630400D24Rik; AI195756; AI606875; AW214352; AW547477; CMD1T; LAP2; LEMD4; PRO0868; RIKEN cDNA 5630400D24 gene; TP; expressed sequence AI195756; expressed sequence AI606875; expressed sequence AW214352; expressed sequence AW547477; lamina-associated polypeptide 2|
|Strain of Origin||129S1/Sv-Oca2<+> Tyr<+> Kitl<+>|
|Molecular Note||At least six alternative transcripts can be derived from this gene locus. This mutation targeted exon 4, which is necessary for generation of a protein product that localizes to the nucleoplasm. A loxP site and a FRT-flanked neomycin cassette was placed upstream of exon 4 and an additional loxP site was placed downstream of the exon. Founder mice were crossed with Cre-deleter mice to remove exon 4 and the neomycin cassette. Homozygote mice lacked the nucleoplasm specific protein isoform but expressed the other protein isoforms as determined by immunoblot analysis of heart and intestinal extracts.|
|Mutations Made By|| |
Roland Foisner, Medical University Vienna
When maintaining a live colony, these mice can be bred as homozygotes.
When using the STOCK Tmpotm1.1Foi/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #010828 in your Materials and Methods section.
|Heterozygous for Tmpo<tm1.1Foi>|
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