Septin 4 (Sept4) homozygous knockout males are sterile due to immotile and structurally defective sperm. Mice also exhibit increased incidence of hematopoietic malignancies having increased numbers of hematopoietic stem and progenitor cells (HSPCs).
Hermann Steller, The Rockefeller University
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Septin4 | septin 4 |
Septin 4 (Sept4) is involved with a variety of cellular functions, including cytokinesis, apoptosis, tumor suppression, and male fertility.
Homozygous knockout mice are viable and born at predicted Mendelian frequencies, but males are sterile due to immotile and structurally defective sperm. Gametes show a complete lack of motility and 50-70% of mutant sperm display a severe L-shaped bending in the tail region. The sperm annulus is completely absent. Sperm isolated from heterozygous animals shows and intermediate phenotype, but their fertility is not significantly reduced.
Mitochondria that localize along the axoneme surrounding the midpiece of sperm contain fewer cristae and vary greatly in size, disrupting their normally regular and precise arrangement in homozygotes. Heterozygotes show no mitochondrial structure abnormalities.
Sperm of homozygous males retains cytoplasmic droplets in the head and neck regions which fail to be eliminated during sperm maturation.
The Sept4 gene also encodes the ARTS isoform which functions as a tumor suppressor. Sept4-null mice exhibit increased incidence of hematopoietic malignancies having increased numbers of hematopoietic stem and progenitor cells (HSPCs). The loss of Sept4 function both promotes spontaneous leukemia/lymphoma and accelerates lymphoma development in an Eμ-Myc background. The incidence of spontaneous hematopoietic malignancies dramatically increased in 11- to 15-mo-old
Sept4-null mice when compared with their wild-type littermates. Approximately one-third of homozygous mutants and almost 10% of the heterozygous mice develop spontaneous neoplasias. Spontaneous tumors in other tissues have also been observed, but they have considerable variation and slow onset (10-14 mo).
Mice deficient for the gene have elevated numbers of hair follicle stem cells (HFSCs) that are protected against apoptosis. Homozygous mice display marked improvement in wound healing and regeneration of hair follicles.
Exons 2-12 were replaced by a PGK-neomycin selection cassette in E14 129P2/OlaHsd-derived embryonic stem (ES) cells. This strain has been backcrossed to C57BL/6 for more than 5 generations by the donating laboratory.
Allele Name | targeted mutation 1, Hermann Steller |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | Sept4- |
Gene Symbol and Name | Septin4, septin 4 |
Gene Synonym(s) | |
Strain of Origin | 129P2/OlaHsd |
Chromosome | 11 |
Molecular Note | 8 kb of sequence, almost the entire locus, was replaced with a neomycin resistance gene. Western blot confirmed the absence of isoforms H5 and M-Septin by probing cerebellum protein extracts from mutants with an antibody raised against a peptide from exon 1. |
Mutations Made By | Hermann Steller, The Rockefeller University |
Homozygous males are not fertile, but heterozygous males and heterozygous/homozygous females are productive. The donating laboratory maintains their colony using homozygous female x heterozygous male crosses.
When using the B6.129P2-Septin4tm1Hs/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #018159 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Sept4<tm1Hs> |
Frozen Mouse Embryo | B6.129P2-Sept4<tm1Hs>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.129P2-Sept4<tm1Hs>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.129P2-Sept4<tm1Hs>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | B6.129P2-Sept4<tm1Hs>/J Frozen Embryo | $3373.50 |
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