Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

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. Species laboratory mouse Background Strain C57BL/6 Donor Strain 129X1 x 129S1 via R1 (+Kitl-SlJ) ES cell line   Donating Investigator Dr. John S. Lazo,   University of Pittsburgh

Description
Bleomycin (BLM) is a clinically used glycopeptide anticancer agent. It is deaminated in vitro by BLMH. Blmh null mice have decreased viability and fertitility. Only about 65% of the expected number survive the neonatal period. Mice lacking Blmh exhibit variably penetrant tail dermatitis that resembles rodent ringtail. This resembles skin lesions in humans with pellagra, necrolytic migratory erythema, and acrodermatitis enteropathica. Null mice also are more sensitive to acute BLM lethality and develop pulmonary fibrosis following BLM treatment.

Control Information

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

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Alzheimer Disease; AD   (BLMH)

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.

Blmh^tm1Geh/Blmh^tm1Geh

        either: (involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6J)

• mortality/aging
• increased sensitivity to xenobiotic induced morbidity/mortality
  • bleomycin doses that were without effect in wild-type mice elicited lethality (50 or 100 mg/kg) in homozygous null mice   (MGI Ref ID J:54585)
• partial neonatal lethality
  • approximately 36% of homozygotes died as neonates; those surviving the neonatal period were fertile and appeared healthy   (MGI Ref ID J:54585)
• behavior/neurological phenotype
• *normal* behavior/neurological phenotype
  • the skin lesions were not caused by aggressive behavior: both male and female mutants were housed individually without resolution of the tail dermatitis   (MGI Ref ID J:54585)
• cardiovascular system phenotype
• *normal* cardiovascular system phenotype
  • homozygotes did not display angitis or vascular thrombosis   (MGI Ref ID J:54585)
• growth/size phenotype
• decreased body size
  • homozygotes frequently appeared smaller than wild-type or heterozygous littermates   (MGI Ref ID J:54585)
• homeostasis/metabolism phenotype
• increased physiological sensitivity to xenobiotic
  • homozygotes were hypersensitive to the deleterious effects of bleomycin   (MGI Ref ID J:54585)
  • bleomycin doses that were without effect in wild-type mice elicited either pulmonary fibrosis (25 mg/kg) in homozygous null mice   (MGI Ref ID J:54585)
• increased sensitivity to xenobiotic induced morbidity/mortality
  • bleomycin doses that were without effect in wild-type mice elicited lethality (50 or 100 mg/kg) in homozygous null mice   (MGI Ref ID J:54585)
• limbs/digits/tail phenotype
• abnormal tail morphology
  • the gross tail lesions resembled rodent ringtail, and were frequently resolved by weaning   (MGI Ref ID J:54585)
• immune system phenotype
• dermatitis
  • dermatitis on the tail only   (MGI Ref ID J:54585)
  • mutants without dermatitis on the tail develop tail dermatitis when kept in a low-humidity atmosphere   (MGI Ref ID J:54585)
• integument phenotype
• dermatitis
  • dermatitis on the tail only   (MGI Ref ID J:54585)
  • mutants without dermatitis on the tail develop tail dermatitis when kept in a low-humidity atmosphere   (MGI Ref ID J:54585)
• scaly skin
  • most newborns appeared normal except for a dermatopathy presenting initially as a mild ichthyosis with generalized scaling and sloughing of the skin over the entire body   (MGI Ref ID J:54585)
  • at ~7-10 days, the scaling became resolved except on the tail   (MGI Ref ID J:54585)
  • no abnormalities were observed in other tissues   (MGI Ref ID J:54585)
• thick epidermis
  • similar to ringtail, the tail dermatitis included thickening of the epidermis (parakeratotic hyperkeratosis and acanthosis), areas of necrosis, and neutrophil infiltrate   (MGI Ref ID J:54585)
  • unlike ringtail, ballooning degeneration of the upper stratum spinosum and palor were observed in some mutant tails   (MGI Ref ID J:54585)

View Research Applications

Research Applications

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

Blmh^tm1Geh related

Cancer Research
Growth Factors/Receptors/Cytokines
Increased Tumor Incidence
      Lymphomas
      Other Tissues/Organs
Toxicology

Dermatology Research
Skin and Hair Texture Defects

Developmental Biology Research
Skin and Hair Texture Defects

Endocrine Deficiency Research
Skin Defects

Immunology, Inflammation and Autoimmunity Research
Inflammation

Internal/Organ Research
Lung Defects

Mouse/Human Gene Homologs
Alzheimer's

Neurobiology Research
Neurodegeneration

Research Tools
Cancer Research
Dermatology Research
Metabolism Research
Toxicology Research
      drug metabolism

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Blmhtm1Geh
Allele Name		targeted mutation 1, Gregg E Homanics
Allele Type		Targeted (knock-out)
Common Name(s)		Bh-; Blmhtm2Geh;
Mutation Made By		Donald Schwartz,   Wayne State Univ School of Medicine
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line Name		R1
ES Cell Line Strain		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name		Blmh, bleomycin hydrolase
Chromosome		11
Gene Common Name(s)		AI035728; BH; BMH; MGC:36899; MGC:37104; MGC:39026; expressed sequence AI035728;
Molecular Note		A genomic fragment containing exon 3 and flanking DNA was replaced with a neomycin selection cassette. The deleted sequences include the region encoding the catalytic cysteine of the protein. Northern blot analysis on total embryonic RNA derived from homozygous mice demonstrated that no transcript was produced from this allele. Western blot and enzymatic activity assays confirmed that no functional protein was made in homozygous mice. [MGI Ref ID J:54585]

Genotyping

Genotyping Information

Genotyping Protocols

Blmh^tm1Geh, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Blmh^tm1Geh related

Montoya SE; Thiels E; Card JP; Lazo JS. 2007. Astrogliosis and behavioral changes in mice lacking the neutral cysteine protease bleomycin hydrolase. Neuroscience 146(3):890-900. [PubMed: 17391860]  [MGI Ref ID J:122060]

Schwartz DR; Homanics GE; Hoyt DG; Klein E; Abernethy J; Lazo JS. 1999. The neutral cysteine protease bleomycin hydrolase is essential for epidermal integrity and bleomycin resistance. Proc Natl Acad Sci U S A 96(8):4680-5. [PubMed: 10200322]  [MGI Ref ID J:54585]

Towne CF; York IA; Watkin LB; Lazo JS; Rock KL. 2007. Analysis of the role of bleomycin hydrolase in antigen presentation and the generation of CD8 T cell responses. J Immunol 178(11):6923-30. [PubMed: 17513741]  [MGI Ref ID J:147841]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Wild-type from the colony
	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.

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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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