JAX Mouse Strain Datasheet - 006241

STOCK Hhip^tm1Amc/J

Stock No:: 006241 |; Hip1-

Targeted Mutation

Cryo Recovery

Overview

Also Known As: Hip1-

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.

Donating Investigator

Andrew P McMahon, University of Southern California

Genetic overview

Genetic Background	Generation

Hhip^tm1Amc

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout, Reporter)	Hhip	Hedgehog-interacting protein

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Research Applications

Cancer Research
Cell Biology Research
Developmental Biology Research
Endocrine Deficiency Research
Immunology, Inflammation and Autoimmunity Research
Internal/Organ Research
Research Tools

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Base Price

Starting at:

$2,595.00 Domestic price Cryo Recovery

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Details

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.

Expression Data

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).

Control Suggestions

Wild-type from the colony

Additional Information

Considerations for Choosing Controls

Selected References

Chuang PT; Kawcak T; McMahon AP. 2003. Feedback control of mammalian Hedgehog signaling by the Hedgehog-binding protein, Hip1, modulates Fgf signaling during branching morphogenesis of the lung. Genes Dev 17(3):342-7. PubMed: 12569124 MGI: J:81798

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Genetics

Hhip^tm1Amc

Allele Symbol: Hhip^tm1Amc

Allele Name	targeted mutation 1, Andrew P McMahon
Allele Type	Targeted (Null/Knockout, Reporter)
Allele Synonym(s)	Hip1-
Gene Symbol and Name	Hhip, Hedgehog-interacting protein
Gene Synonym(s)	HIP; Hhip1; Hip; Hip1; RGD1564108
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

Disease/Phenotype

Disease Terms

Research Areas By Genotype

This mouse can be used to support research in many areas including:

Cancer Research
- Genes Regulating Growth and Proliferation
- Growth Factors/Receptors/Cytokines
Cell Biology Research
- Genes Regulating Growth and Proliferation
Developmental Biology Research
- Growth Defects
  - Growth Defects (homozygous)
- Internal/Organ Defects
  - lung
- Perinatal Lethality
  - Homozygous
- Skeletal Defects
Endocrine Deficiency Research
- Pancreas Defects
Immunology, Inflammation and Autoimmunity Research
- Growth Factors/Receptors/Cytokines
Internal/Organ Research
- Lung Defects
Research Tools
- lacZ Expression
- Genetics Research
  - Tissue/Cell Markers
  - Tissue/Cell Markers: multiple

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Hhip^tm1Amc/Hhip^tm1Amc
involves: 129S1/Sv * 129X1/SvJ

mortality/aging

neonatal lethality, complete penetrance
- homozygotes die in the first hours after birth due to respiratory failure

cellular phenotype

decreased pancreatic beta cell proliferation
- slight but significant decrease in proliferative activity of beta cells

respiratory system phenotype

abnormal lung morphology

abnormal pulmonary alveolar duct morphology
- failed branching pattern, lateral bulges appear at E11.5 but branching does not continue
- proximodistal patterning normal
- reduced airway space and increased number of mesenchymal cells

left pulmonary isomerism
- only one right lung lobe, corresponding to single left lung lobe

primary atelectasis
- lungs fail to inflate at birth

respiratory failure
- ultimate cause of death

small lung
- lungs 1/4 to 1/3 normal size

nervous system phenotype

abnormal neural tube morphology
- normal neural tube
- small but significant expansion of ventral neuronal progenitors

digestive/alimentary phenotype

abnormal stomach glandular epithelium morphology
- reduced in thickness while stomach mesenchyme increases

hematopoietic system phenotype

abnormal spleen morphology
- deformed at E18.5

small spleen
- reduced in mass at E18.5

immune system phenotype

abnormal spleen morphology
- deformed at E18.5

small spleen
- reduced in mass at E18.5

endocrine/exocrine gland phenotype

abnormal pancreas development
- in severe cases, E18.5 dorsal and ventral pancreases fuse into a compact mass smaller in size than normal
- normal architecture of acinar cells
- ventral pancreas tissue, normally attached to the dorsal region of the duodenum, extends ventrally towards the mediolateral area of the duodenum

abnormal pancreatic islet morphology
- disorganized and reduced in size, cross sectional area reduced 45%

decreased pancreatic beta cell proliferation
- slight but significant decrease in proliferative activity of beta cells

disorganized pancreatic islets

ectopic pancreas
- at E18.5, some mutants display ectopic pancreas formation with patches of pancreatic tissue incorporated into the duodenum

small pancreatic islets

growth/size/body region phenotype

left pulmonary isomerism
- only one right lung lobe, corresponding to single left lung lobe

embryo phenotype

abnormal neural tube morphology
- normal neural tube
- small but significant expansion of ventral neuronal progenitors

References

Chuang PT; Kawcak T; McMahon AP. 2003. Feedback control of mammalian Hedgehog signaling by the Hedgehog-binding protein, Hip1, modulates Fgf signaling during branching morphogenesis of the lung. Genes Dev 17(3):342-7. PubMed: 12569124 MGI: J:81798

Additional - Hhip^tm1Amc related

Holtz AM; Griffiths SC; Davis SJ; Bishop B; Siebold C; Allen BL. 2015. Secreted HHIP1 interacts with heparan sulfate and regulates Hedgehog ligand localization and function. J Cell Biol 209(5):739-57. PubMed: 26056142 MGI: J:227320
Jeong J; McMahon AP. 2005. Growth and pattern of the mammalian neural tube are governed by partially overlapping feedback activities of the hedgehog antagonists patched 1 and Hhip1. Development 132(1):143-54. PubMed: 15576403 MGI: J:94269
Kawahira H; Ma NH; Tzanakakis ES; McMahon AP; Chuang PT; Hebrok M. 2003. Combined activities of hedgehog signaling inhibitors regulate pancreas development. Development 130(20):4871-9. PubMed: 12917290 MGI: J:85472
Lao T; Glass K; Qiu W; Polverino F; Gupta K; Morrow J; Mancini JD; Vuong L; Perrella MA; Hersh CP; Owen CA; Quackenbush J; Yuan GC; Silverman EK; Zhou X. 2015. Haploinsufficiency of Hedgehog interacting protein causes increased emphysema induced by cigarette smoke through network rewiring. Genome Med 7(1):12. PubMed: 25763110 MGI: J:241971
Lao T; Jiang Z; Yun J; Qiu W; Guo F; Huang C; Mancini JD; Gupta K; Laucho-Contreras ME; Naing ZZ; Zhang L; Perrella MA; Owen CA; Silverman EK; Zhou X. 2016. Hhip haploinsufficiency sensitizes mice to age-related emphysema. Proc Natl Acad Sci U S A 113(32):E4681-7. PubMed: 27444019 MGI: J:235299
Yam PT; Kent CB; Morin S; Farmer WT; Alchini R; Lepelletier L; Colman DR; Tessier-Lavigne M; Fournier AE; Charron F. 2012. 14-3-3 proteins regulate a cell-intrinsic switch from sonic hedgehog-mediated commissural axon attraction to repulsion after midline crossing. Neuron 76(4):735-49. PubMed: 23177959 MGI: J:196985

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous or wildtype for Hhip<tm1Amc>

Progeny testing is not required

The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks.

The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

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Frozen Mouse Embryo

$2,595.00 per straw or vial

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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.

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Licensing Information

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Also Known As: Hip1-

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Hhiptm1Amc

Allele Symbol: Hhiptm1Amc

Disease Terms

Research Areas By Genotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Hhiptm1Amc/Hhiptm1Amcinvolves: 129S1/Sv * 129X1/SvJ

mortality/aging

cellular phenotype

respiratory system phenotype

nervous system phenotype

digestive/alimentary phenotype

hematopoietic system phenotype

immune system phenotype

endocrine/exocrine gland phenotype

growth/size/body region phenotype

embryo phenotype

References

Additional - Hhiptm1Amc related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Progeny testing is not required

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Hhip^tm1Amc

Allele Symbol: Hhip^tm1Amc

Genotype: Hhip^tm1Amc/Hhip^tm1Amc
involves: 129S1/Sv * 129X1/SvJ

Additional - Hhip^tm1Amc related