Loss of Hhip1 function in these mice results in specific defects in two Hedgehog target issues, the lung, a target of Sonic hedgehog (Shh) signaling, and the endochondral skeleton, a target of Indian hedgehog (Ihh) signaling.
Andrew P McMahon, University of Southern California
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Reporter, Null/Knockout) | Hhip | Hedgehog-interacting protein |
Mice heterozygous for this targeted mutation are viable and fertile. Homozygotes die from respiratory failure shortly after birth. Expression of the "knocked-in" lacZ gene is detected in a pattern similar to the endogenous transcript (in lung, skeleton, stomach, duodenum, spleen, and pancreas), and serves as a faithful reporter for Hedgehog (Hh) signaling. Because Hh and fibroblast growth factor (Fgf) signaling are abnormal, homozygous mice have defects in many Hh target tissues. Although the primary lung buds form in homozygotes, lung branching morphogenesis is defect beginning at 10.5 days postcoitus (dpc), and fails to generate a complete respiratory tree. The single left lobe also is significantly reduced, and total lung size at birth is diminished 67-75% compared to wildtype. In addition, homozygous mice have delayed mineralization of the endochondral skeleton, as well as impaired pancreas morphogenesis, islet formation and endocrine cell proliferation. These mutant mice may be useful in studies of Hh and Fgf signaling, organ/tissue development, and cancer.
A targeting vector was designed to replace exon 1 of the endogenous gene with a beta-galactosidase (lacZ) gene and PGK-neo cassette. This construct was microinjected into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. Chimeric mice were bred to either C57BL/6 inbred and/or Swiss-Webster outbred mice to establish heterozygous mutants. Heterozygous mice were bred together (generating mutant mice on a mixed C57BL/6, Swiss-Webster, 129 genetic background) for many generations before arrival at The Jackson Laboratory.
Expressed Gene | lacZ, beta-galactosidase, E. coli |
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Site of Expression | Expression of the lacZ knockin gene is detected in lung, skeleton, stomach, duodenum, spleen, and pancreas). |
Allele Name | targeted mutation 1, Andrew P McMahon |
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Allele Type | Targeted (Reporter, Null/Knockout) |
Allele Synonym(s) | Hip1- |
Gene Symbol and Name | Hhip, Hedgehog-interacting protein |
Gene Synonym(s) | |
Expressed Gene | lacZ, beta-galactosidase, E. coli |
Site of Expression | Expression of the lacZ knockin gene is detected in lung, skeleton, stomach, duodenum, spleen, and pancreas). |
Strain of Origin | (129X1/SvJ x 129S1/Sv)F1-Kitl+ |
Chromosome | 8 |
Molecular Note | The endogenous locus was disrupted by the insertion of cassette containing lacZ and PGK-neo genes. The start codon and downstream sequences were deleted from exon 1. The expression pattern of beta-galactosidase was similar to that of the endogenous gene. |
Mutations Made By | Andrew McMahon, University of Southern California |
When maintaining a live colony, heterozygous mice are bred together or to wildtype siblings. Homozygotes die immediately after birth from respiratory failure.
When using the Hip1- mouse strain in a publication, please cite the originating article(s) and include JAX stock #006241 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Hhip<tm1Amc> |
Frozen Mouse Embryo | STOCK Hhip<tm1Amc>/J Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | STOCK Hhip<tm1Amc>/J Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | STOCK Hhip<tm1Amc>/J Frozen Embryos | $3373.50 |
Frozen Mouse Embryo | STOCK Hhip<tm1Amc>/J Frozen Embryos | $3373.50 |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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