STOCK Hhip^tm1Amc/J

Stock number: 006241
Product name: Hip1-
Research areas: Cancer Research, Cell Biology Research, Developmental Biology Research, Endocrine Deficiency Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools

Description

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.

Detailed description

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.

Development

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.

Allele

Symbol: Hhip^tm1Amc
Name: targeted mutation 1, Andrew P McMahon
MGI accession ID: MGI:2450891
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Marker symbol: Hhip
Marker name: Hedgehog-interacting protein
Chromosome: 8
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Expressed genes: lacZ,beta-galactosidase,E. coli
Site of expression: Expression of the lacZ knockin gene is detected in lung, skeleton, stomach, duodenum, spleen, and pancreas).
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.