Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Homozygote x Homozygote         (Female x Male)   25-JAN-13 Species laboratory mouse Generation ?+F2 (07-JAN-13) Generation Definitions   Donating Investigator Michael Bustin,   NIH

Description
Mice that are homozygous for the targeted mutation are viable and fertile. Certain antibodies to HMGN1 detect a short version of HMGN1 protein by Western blot analysis when large amounts of MEFs from homozygous animals are analyzed. Mice homozygous for this targeted mutation, and on a congenic C57BL/6 background, do not exhibit the perinatal lethality seen in homozygotes on the 129 and mixed B6;129 backgrounds. Homozygotes exhibit increased histone acetylation in brain tissue, and reduced levels of exploratory behavior and preference for social novelty. MEFs isolated from homozygous mice on the congenic C57BL/6 background exhibit defective DNA repair. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6J genetic background.

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. This is the case for the strain above. 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 containing a NEO cassette was used to disrupt exons 2, 3 and part of exon 4. The construct was electroporated into 129X1/SvJ derived ESVJ-1183 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice, and then backcrossed to C57BL/6J for 10 generations, using a speed congenic protocol. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

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

Hmgn1^tm1Mbus/Hmgn1⁺

        involves: 129X1/SvJ

• mortality/aging
• increased mortality induced by gamma-irradiation
  • 1 year after sublethal gamma-irradiation only 49% of heterozygous mice survive compared to 75% of wild-type littermates   (MGI Ref ID J:100773)
• cellular phenotype
• increased cellular sensitivity to gamma-irradiation
  • primary MEFs are more sensitive to gamma-irradiation induced death compared to wild-type cells but less sensitive than homozygous cells   (MGI Ref ID J:100773)

Hmgn1^tm1Mbus/Hmgn1⁺

        either: (involves: 129/Sv * 129X1/SvJ) or (involves: 129/Sv * 129X1/SvJ * C57BL/6)

• cellular phenotype
• increased cellular sensitivity to ultraviolet irradiation
  • primary MEFs are more sensitive to UV-C irradiation induced death compared to wild-type cells but less sensitive than homozygous cells   (MGI Ref ID J:100282)

Hmgn1^tm1Mbus/Hmgn1^tm1Mbus

        either: (involves: 129/Sv * 129X1/SvJ) or (involves: 129/Sv * 129X1/SvJ * C57BL/6)

• mortality/aging
• partial embryonic lethality during organogenesis
  • at E11.5 only 8% of mice are homozygous rather than the expected 25%   (MGI Ref ID J:100282)
• cellular phenotype
• abnormal cell physiology
  • in primary MEFs, the removal of UV induced cyclobutane pyrimidine dimers is slower than in wild-type cells   (MGI Ref ID J:100282)
• • increased cellular sensitivity to ultraviolet irradiation
    • primary MEFs are more sensitive to UV-C irradiation induced death (D50 = 3 J/m2 compared to 13.5 J/m2 for wild-type cells)   (MGI Ref ID J:100282)
• integument phenotype
• increased sensitivity to skin irradiation
  • a cumulative UV-B dose of 1200 J/m2 produces skin alterations including acanthosis and localized hyperkeratosis in homozygotes but not in wild-type mice   (MGI Ref ID J:100282)

Hmgn1^tm1Mbus/Hmgn1^tm1Mbus

        involves: 129X1/SvJ

• mortality/aging
• increased mortality induced by gamma-irradiation
  • 1 year after sublethal gamma-irradiation only 45% of homozygous mice survive compared to 75% of wild-type littermates   (MGI Ref ID J:100773)
• cellular phenotype
• abnormal cell cycle checkpoint function
  • 1 hour after gamma-irradiation with 0.6 Gy homozygous cells do not delay entry into mitosis unlike wild-type cells   (MGI Ref ID J:100773)
• increased cell proliferation
  • the doubling time of primary MEFs is only 12 hours compared to 19 hours in wild-type cells   (MGI Ref ID J:100773)
  • homozygous cells reach senescence at passage 13 rather than passage 8 as in wild-type cells   (MGI Ref ID J:100773)
• increased cellular sensitivity to gamma-irradiation
  • primary MEFs are more sensitive to gamma-irradiation induced death (D50 = 3.5 Gy compared to greater than 7 Gy for wild-type cells)   (MGI Ref ID J:100773)
• tumorigenesis
• increased metastatic potential
  • at 1 year of age 25% of male homozygotes had malignant tumors that metastasized compared to 0% of wild-type males   (MGI Ref ID J:100773)
• increased tumor incidence
  • at 1 year of age over 40% of homozygotes have multiple tumors compared to 17% and 27% of wild-type males and females, respectively   (MGI Ref ID J:100773)
  • life span and average age of tumor detection are not different from wild-type; however in mice that die young tumors were detected at significantly younger ages in homozygotes compared to wild-type mice   (MGI Ref ID J:100773)
  • a marginal increase in the incidence of hematopoietic and hepatic neoplasms, as well as occurrence of unusual tumors (granule cell tumors of the brain, jejunal carcinoma, and renal tubule neoplasms) are seen   (MGI Ref ID J:100773)
• • hemangioma
    • a marginal increase in the incidence of hemangiosarcomas is seen   (MGI Ref ID J:100773)
  • increased incidence of ionizing radiation-induced tumors
    • of the mice that die within 1 year 90% have tumors usually a large thymic mass indicating an increase in the incidence of lymphomas   (MGI Ref ID J:100773)
  • malignant tumors
    • at 1 year of age 58% of male and 82% of female homozygotes have malignant tumors compared to 29% and 55% of wild-type males and females, respectively   (MGI Ref ID J:100773)
  • pheochromocytoma
    • the frequency of endocrine tumors, including adrenal pheochromocytoma, are increased   (MGI Ref ID J:100773)

View Research Applications

Research Applications

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

Cancer Research
Other
      DNA Repair

Cell Biology Research
DNA Damage Response

Neurobiology Research
Behavioral and Learning Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Hmgn1tm1Mbus
Allele Name		targeted mutation 1, Michael Bustin
Allele Type		Targeted (knock-out)
Common Name(s)		Hmgn1-;
Mutation Made By		Michael Bustin,   NIH
Strain of Origin		129X1/SvJ
Gene Symbol and Name		Hmgn1, high mobility group nucleosomal binding domain 1
Chromosome		16
Gene Common Name(s)		HMG-14; Hmg14; high mobility group protein 14;
Molecular Note		Exons 2, 3 and part of 4 were replaced with a neomycin resistance cassette. Western blot of mutant MEFs confirmed absence of protein. Heterozygotes expressed approximately half of that detected in wild-type cells. [MGI Ref ID J:100282]

Genotyping

Genotyping Information

Genotyping Protocols

Hmgn1^tm1Mbus, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Birger Y; West KL; Postnikov YV; Lim JH; Furusawa T; Wagner JP; Laufer CS; Kraemer KH; Bustin M. 2003. Chromosomal protein HMGN1 enhances the rate of DNA repair in chromatin. EMBO J 22(7):1665-75. [PubMed: 12660172]  [MGI Ref ID J:100282]

Additional References

Hmgn1^tm1Mbus related

Abuhatzira L; Shamir A; Schones DE; Schaffer AA; Bustin M. 2011. The Chromatin-binding Protein HMGN1 Regulates the Expression of Methyl CpG-binding Protein 2 (MECP2) and Affects the Behavior of Mice. J Biol Chem 286(49):42051-62. [PubMed: 22009741]  [MGI Ref ID J:178717]

Belova GI; Postnikov YV; Furusawa T; Birger Y; Bustin M. 2008. Chromosomal protein HMGN1 enhances the heat shock-induced remodeling of Hsp70 chromatin. J Biol Chem 283(13):8080-8. [PubMed: 18218636]  [MGI Ref ID J:135286]

Birger Y; Catez F; Furusawa T; Lim JH; Prymakowska-Bosak M; West KL; Postnikov YV; Haines DC; Bustin M. 2005. Increased tumorigenicity and sensitivity to ionizing radiation upon loss of chromosomal protein HMGN1. Cancer Res 65(15):6711-8. [PubMed: 16061652]  [MGI Ref ID J:100773]

Birger Y; Davis J; Furusawa T; Rand E; Piatigorsky J; Bustin M. 2006. A role for chromosomal protein HMGN1 in corneal maturation. Differentiation 74(1):19-29. [PubMed: 16466397]  [MGI Ref ID J:105284]

Furusawa T; Ko JH; Birger Y; Bustin M. 2009. Expression of nucleosomal protein HMGN1 in the cycling mouse hair follicle. Gene Expr Patterns :. [PubMed: 19303948]  [MGI Ref ID J:148798]

Kim YC; Gerlitz G; Furusawa T; Catez F; Nussenzweig A; Oh KS; Kraemer KH; Shiloh Y; Bustin M. 2009. Activation of ATM depends on chromatin interactions occurring before induction of DNA damage. Nat Cell Biol 11(1):92-6. [PubMed: 19079244]  [MGI Ref ID J:176195]

Masaoka A; Gassman NR; Kedar PS; Prasad R; Hou EW; Horton JK; Bustin M; Wilson SH. 2012. HMGN1 protein regulates poly(ADP-ribose) polymerase-1 (PARP-1) self-PARylation in mouse fibroblasts. J Biol Chem 287(33):27648-58. [PubMed: 22736760]  [MGI Ref ID J:190250]

Rochman M; Taher L; Kurahashi T; Cherukuri S; Uversky VN; Landsman D; Ovcharenko I; Bustin M. 2011. Effects of HMGN variants on the cellular transcription profile. Nucleic Acids Res 39(10):4076-87. [PubMed: 21278158]  [MGI Ref ID J:182874]

Yang D; Postnikov YV; Li Y; Tewary P; de la Rosa G; Wei F; Klinman D; Gioannini T; Weiss JP; Furusawa T; Bustin M; Oppenheim JJ. 2012. High-mobility group nucleosome-binding protein 1 acts as an alarmin and is critical for lipopolysaccharide-induced immune responses. J Exp Med 209(1):157-71. [PubMed: 22184635]  [MGI Ref ID J:181721]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX18

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice can be bred as homozygotes.
Mating System	Homozygote x Homozygote         (Female x Male)   25-JAN-13
Diet Information	LabDiet® 5K20

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

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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