Khdrbs1 KO mice display partial perinatal lethality, a lean phenotype and are protected against dietary induced obesity. Bone mass is preserved with age such that age-induced osteoporosis does not develop.
Stephane Richard, McGill University
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Khdrbs1 | KH domain containing, RNA binding, signal transduction associated 1 |
Khdrbs1 (also known as Sam68 or STAR) is a KH type RNA-binding protein known to be phosphorylated, arginine methylated, sumoylated and acetylated. This RNA binding protein is involved in alternative spicing, protein translation, and signal transduction.
Homozygous Khdrbs1/Sam68 null mice display a lean phenotype and are protected against dietary induced obesity (DIO). In addition, they preserve their bone mass with age and do not develop age-induced osteoporosis. Offspring from heterozygote intercrosses exhibit a Mendelian segregation, but some of the homozygous pups die at birth of unknown causes. Homozygotes that survive the perinatal period frequently live to old age (> 2 years).
Ablation of the Khdrbs1 gene leads to male infertility due to several defects in spermatogenesis. Homozygous females are subfertile, exhibiting uterine development defects and delayed mammary gland development. They also fail to care for their young successfully.
Haploinsufficiency of the Khdrbs1 impedes mammary tumor onset in vivo and metastasis driven by the potent mammary-targeted polyoma middle T-antigen (MMTV-PyMT) oncogene.
Homozygous Khdrbs1 knockout mice exhibit motor coordination defects as assessed by beam walking and rotorod performance. Forelimb strength is normal, as is tail-hang reflex, balance test, grid walking, the Morris water task, recognition memory, visual discrimination, auditory stimulation and conditional taste aversion.
Exon 4 and part of exon 5 were replaced with a PGK-Neo cassette in (129X1/SvJ x 129S1/Sv)F1- Kitl+-derived R1 embryonic stem (ES) cells. Chimeric mice were bred to BALB/c animals, then to C57BL/6 for at least 12 generations by the donating laboratory.
Allele Name | targeted mutation 1, Stephane Richard |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | Sam68- |
Gene Symbol and Name | Khdrbs1, KH domain containing, RNA binding, signal transduction associated 1 |
Gene Synonym(s) | |
Strain of Origin | (129X1/SvJ x 129S1/Sv)F1-Kitl+ |
Chromosome | 4 |
Molecular Note | A PGK-neo cassette in reverse orientation replaced exon 4 and most of exon 5. Western blot confirmed absence of protein in mutants. |
Many of the homozygous pups die at birth of unknown causes. Surviving homozygous males are infertile due to several defects in spermatogenesis. Homozygous females are severely subfertile, have uterine development defects, and show delayed mammary gland development.
When using the B6.129(C)-Khdrbs1tm1Rchd/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #018444 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Khdrbs1<tm1Rchd> |
Frozen Mouse Embryo | B6.129(C)-Khdrbs1<tm1Rchd>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.129(C)-Khdrbs1<tm1Rchd>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.129(C)-Khdrbs1<tm1Rchd>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | B6.129(C)-Khdrbs1<tm1Rchd>/J Frozen Embryo | $3373.50 |
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