Description

Strain Information

Type Congenic; Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System +/+ sibling x Heterozygote         (Female x Male) Species laboratory mouse Generation N11+ (19-AUG-08)   Donating Investigator Michael Bates,   Cincinnati Children's Hospital Med Ctr

Description
Homozygous null mice have an embryonic lethal phenotype. Homozygous mice on the C57BL/6 and B6;129 mixed background fail to develop past embryonic days 15.5 due to impaired fetal hematopoiesis (anemia, hypoplastic and abnormal development of the liver, hypoplastic gut). Homozygous mice on the FVB/N background survive through embryonic day 18.5 and dead homozygote newborn pups are observed. Late gestation homozygous embryos on the FVB/N background are smaller than wildtype littermates, pale, hydropic (subcutaneous fluid ballooning skin), and have impaired neural crest cell and enteric neuron migration from the stomach to intestine. Mice that are heterozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Naive CD4 T cells from heterozygotes exhibit increased responsiveness to IL-4, resulting in differentiation of more Th2 cells. This mutant mouse strain may be useful in studies of liver and gastrointestinal development and T helper 2 cell differentiation.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt a portion of exon 4 encoding the homeo box. The construct was electroporated into 129P2/OlaHsd derived E14 embryonic stem (ES) cells. Correctly targeted ES cells were injected into (C57BL/6 x C57BL/10)F1 blastocysts. The resulting chimeric animals were interbred before being crossed to C57BL/6 mice, and then backcrossed to C57BL/6 for 10 generations.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying   Hlx^tm1Rph allele

008315

FVB.129P2(Cg)-Hlxtm1Rph/J

View Strains carrying   Hlx^tm1Rph     (1 strain)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Hlx^tm1Rph/Hlx^tm1Rph

        involves: 129P2/OlaHsd

• lethality-prenatal/perinatal
• embryonic lethality during organogenesis (MGI Ref ID J:31553)
  • embryos are dead by E15
  • defects in organogenesis although embryo size normal
• liver/biliary system phenotype
• abnormal liver development (MGI Ref ID J:31553)
  • liver development starts normally at about E9
  • no liver buds formed by E10.5
  • at E14.5 liver composed of a small dorsal bud and very rudimentary ventral lobe
  • general architecture and cell composition normal at E14.5
  • hepatocyte differentiation normal
• absent gall bladder (MGI Ref ID J:31553)
• liver hypoplasia (MGI Ref ID J:31553)
  • liver minute in size at death
  • at E12.5 only 3% of normal number of cells
• digestive/alimentary phenotype
• abnormal intestine morphology (MGI Ref ID J:31553)
  • gut appears normal at E10.5
  • only a single intestinal loop at E13.5 and E14.5 as opposed to more extensive looping in controls
  • intestine only about 1/4 normal length at death
• small pancreas (MGI Ref ID J:31553)
  • pancreas reduced in size but otherwise normal
• hematopoietic system phenotype
• abnormal erythropoiesis (MGI Ref ID J:31553)
  • erythroid precursors in liver at normal proportions but low absolute numbers
• anemia (MGI Ref ID J:31553)
  • at E13.5
  • embryos pallid at death
• impaired hematopoiesis (MGI Ref ID J:31553)
  • hematopoietic cells function normally when transplanted
  • proportion of multilinear precursors is reduced
  • deficient fetal hematopoiesis which occurs in the liver starting around E10
  • yolk sac hematopoesis is normal
• respiratory system phenotype
• enlarged lung (MGI Ref ID J:31553)
  • appear somewhat enlarged and protrude through the diaphragm
• muscle phenotype
• abnormal diaphragm morphology (MGI Ref ID J:31553)
  • contains few muscle cells
• herniated diaphragm (MGI Ref ID J:31553)
• endocrine/exocrine gland phenotype
• small pancreas (MGI Ref ID J:31553)
  • pancreas reduced in size but otherwise normal

Hlx^tm1Rph/Hlx^tm1Rph

        FVB.129P2-Hlx^tm1Rph

• lethality-prenatal/perinatal
• perinatal lethality (MGI Ref ID J:119681)
  • mutants on the FVB/N background survive longer (embryos are seen through E18.5 and only newborn pups are found dead) than mutants on a 129P2/OlaHsd background (die around E15.5)
• growth/size phenotype
• reduced fetal size (MGI Ref ID J:119681)
  • late-gestation embryos are small
• nervous system phenotype
• abnormal enteric neuron morphology (MGI Ref ID J:119681)
  • marker analysis of the intestinal mesenchyme from E10.5 to E16.5 shows that neural crest cells/early enteric neurons are largely absent in the intestine
• liver/biliary system phenotype
• abnormal liver development (MGI Ref ID J:119681)
  • lack hepatic development
• homeostasis/metabolism phenotype
• hydrops fetalis (MGI Ref ID J:119681)
  • late-gestation embryos exhibit hydrops, with the skin ballooning by subcutaneous fluid
• hypoalbuminemia (MGI Ref ID J:119681)
  • decease in serum albumin concentrations
• skin/coat/nails phenotype
• pallor (MGI Ref ID J:119681)
  • late-gestation embryos are pale

View Research Applications

Research Applications

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

Developmental Biology Research
Internal/Organ Defects (liver)
Lymphoid Tissue Defects (hematopoietic defects)

Hematological Research
Hematopoietic Defects
Immunological Defects

Immunology and Inflammation Research
Lymphoid Tissue Defects (hematopoietic development)

Internal/Organ Research
Gastrointestinal Defects
Liver Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Hlxtm1Rph
Allele Name		targeted mutation 1, Richard P Harvey
Allele Type		Targeted (knock-out)
Common Name(s)		Hlx-/-;
Mutation Made By		Michael Bates,   Cincinnati Children's Hospital Med Ctr
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		E14
ES Cell Line Strain		129P2/OlaHsd
Gene Symbol and Name		Hlx, H2.0-like homeobox
Chromosome		1
Gene Common Name(s)		H2.0-like homeo box 1 (Drosophila); HB24; HLX1; Hlx1; MGC156701;
Molecular Note		The insertion of a neomycin selection cassette deleted the sequence encoding the DNA-binding helix 3 of the homeodomain. [MGI Ref ID J:31553]

Genotyping

Genotyping Information

Genotyping Protocols

Hlx^tm1Rph, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Hentsch B; Lyons I; Li R; Hartley L; Lints TJ; Adams JM; Harvey RP. 1996. Hlx homeo box gene is essential for an inductive tissue interaction that drives expansion of embryonic liver and gut. Genes Dev 10(1):70-9. [PubMed: 8557196]  [MGI Ref ID J:31553]

Additional References

Hlx^tm1Rph related

Bates MD; Dunagan DT; Welch LC; Kaul A; Harvey RP. 2006. The Hlx homeobox transcription factor is required early in enteric nervous system development. BMC Dev Biol 6:33. [PubMed: 16854219]  [MGI Ref ID J:119681]

Mikhalkevich N; Becknell B; Caligiuri MA; Bates MD; Harvey R; Zheng WP. 2006. Responsiveness of naive CD4 T cells to polarizing cytokine determines the ratio of Th1 and Th2 cell differentiation. J Immunol 176(3):1553-60. [PubMed: 16424184]  [MGI Ref ID J:126429]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice can be bred as heterozygotes. Homozygotes have an embryonic lethal phenotype.
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 eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
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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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries

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

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

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MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.