Description

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System +/+ sibling x Heterozygote         (Female x Male) Species laboratory mouse Generation F?+1 (30-OCT-08)   Donating Investigator Shihua Li,   Emory University School of Medicine

Description
Mice homozygous for this Huntingtin Associated Protein (HAP1)-deficient allele have neurodegeneration in areas of the hypothalamus that control feeding behavior, resulting in decreased feeding behavior, dehydration, hypoactivity, and death between two and 15 days after birth. No protein expression from the targeted gene is observed in brain tissue from homozygous mice. Hypothalamus tissue from HAP1-deficient homozygotes exhibit reduced levels of gamma-aminobutyric acid-A (GABA_A; a neurotransmitter associated with feeding) and tropomyosin-related kinase A receptor tyrosine kinase (TrkA; a nerve growth factor receptor associated with neurite outgrowth). Heterozygous mice are viable and fertile with no abnormalities in HAP1 expression levels, life span, behavior, and body weight. These huntingtin-associated protein-1 (HAP1) mutant mice may be useful in studying the hypothalamic neurodegeneration and loss of body weight in Huntingon's disease (HD), neurotransmitters, microtubule-dependent transporters, intracellular trafficking, receptor tyrosine kinase and neurite function, and feeding.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. These mice were originally published on a mixed Black Swiss and 129S6/SvEvTac genetic background. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development
A targeting vector was designed to replace the first two exons (first 131 amino acids) of the targeted gene with a neomycin cassette. The construct was electroporated into 129S6/SvEvTac-derived TC-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient C57BL/6 blastocysts. The resulting chimeric males were bred with Black Swiss females to generate mutant offspring. These HAP1 mutant mice were maintained on a mixed genetic background ("129S6Ev/Black Swiss" and possibly "SV129BL/6") for many generations prior to arrival at The Jackson Laboratory. Upon arrival at The Jackson Laboratory, these mice may have been bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

NOT	Huntington Disease; HD - No similarity to the expected human disease phenotype was found.4

4 One or more human genes are associated with this human disease. The mouse genotype may involve mutations to orthologs of one or more of those genes, but the phenotype did not resemble the disease.

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Hap1^tm1Xjl/Hap1^tm1Xjl

        involves: 129S6/SvEvTac * Black Swiss

• lethality-postnatal
• postnatal lethality (MGI Ref ID J:84682)
  • most mice died 3 to 4 days after birth
  • no mice survived longer than 15 days of age
• behavior/neurological phenotype
• *normal* behavior/neurological phenotype (MGI Ref ID J:84682)
  • mice that survived to 9 days of age did not exhibit motor control defects
• abnormal eating behavior (MGI Ref ID J:84682)
  • pups had very little milk in their stomachs
• growth/size phenotype
• decreased body weight (MGI Ref ID J:84682)
• postnatal growth retardation (MGI Ref ID J:84682)
  • mice were unable to gain weight after birth
• nervous system phenotype
• abnormal hypothalamus morphology (MGI Ref ID J:84682)
  • degeneration of the hypothalamus in regions that control feeding behavior
• neurodegeneration (MGI Ref ID J:84682)
  • degeneration observed in regions of the hypothalamus

View Research Applications

Research Applications

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

Cell Biology Research
Channel and Transporter Defects
Signal Transduction
Vesicular Trafficking

Developmental Biology Research
Perinatal Lethality (Homozygous)

Mouse/Human Gene Homologs
Huntington's disease (chorea)

Neurobiology Research
Channel and Transporter Defects
Huntington's disease
Neurodegeneration
Neurodevelopmental Defects
Neurotransmitter Receptor and Synaptic Vesicle Defects
Receptor Defects

Research Tools
Cell Biology Research
Neurobiology Research

Genes & Alleles

Gene & Allele Information

Allele Symbol		Hap1tm1Xjl
Allele Name		targeted mutation 1, Xiao-Jiang Li
Allele Type		Targeted (knock-out)
Common Name(s)		HAP1-;
Mutation Made By		Xiao-Jiang Li,   Emory University School of Medicine
Strain of Origin		129S6/SvEvTac
ES Cell Line Name		TC-1
ES Cell Line Strain		129S6/SvEvTac
Gene Symbol and Name		Hap1, huntingtin-associated protein 1
Chromosome		11
Gene Common Name(s)		HAP-1; HAP2; HIP5; HLP; hHLP1;
Molecular Note		Exons 1 and 2, which encode the first 131 amino acids, were replaced with a neomycin selection cassette. Protein was undetected in the brains of homozygous mutant mice by Western blot analysis. [MGI Ref ID J:84682]

Genotyping

Genotyping Information

Genotyping Protocols

Hap1^tm1Xjl, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Li SH; Yu ZX; Li CL; Nguyen HP; Zhou YX; Deng C; Li XJ. 2003. Lack of huntingtin-associated protein-1 causes neuronal death resembling hypothalamic degeneration in Huntington's disease. J Neurosci 23(17):6956-64. [PubMed: 12890790]  [MGI Ref ID J:84682]

Rong J; McGuire JR; Fang ZH; Sheng G; Shin JY; Li SH; Li XJ. 2006. Regulation of intracellular trafficking of huntingtin-associated protein-1 is critical for TrkA protein levels and neurite outgrowth. J Neurosci 26(22):6019-30. [PubMed: 16738245]  [MGI Ref ID J:128472]

Sheng G; Chang GQ; Lin JY; Yu ZX; Fang ZH; Rong J; Lipton SA; Li SH; Tong G; Leibowitz SF; Li XJ. 2006. Hypothalamic huntingtin-associated protein 1 as a mediator of feeding behavior. Nat Med 12(5):526-33. [PubMed: 16604089]  [MGI Ref ID J:109572]

Additional References

Hap1^tm1Xjl related

Sheng G; Xu X; Lin YF; Wang CE; Rong J; Cheng D; Peng J; Jiang X; Li SH; Li XJ. 2008. Huntingtin-associated protein 1 interacts with Ahi1 to regulate cerebellar and brainstem development in mice. J Clin Invest 118(8):2785-95. [PubMed: 18636121]  [MGI Ref ID J:140869]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, heterozygous mice are bred to wildtype siblings. Homozygous mice die between 2 and 15 days after birth.
Mating System	+/+ sibling x Heterozygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and six weeks of age. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

The Jackson Laboratory's Genotype Promise

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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Ordering and Purchasing Information

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Contact Information
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Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Strain(s) not available to companies or for-profit entities.

Contact information

General inquiries

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phone:	207-288-6470
fax:	207-288-6655

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