Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Background Strain C57BL/6 Donor Strain 129X1 x 129S1 via R1 (+Kitl-SlJ) ES cell line Generation N9   Donating Investigator John 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

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.

Blmh^tm1Geh/Blmh^tm1Geh

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

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

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)
Increased Tumor Incidence (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 and Inflammation 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

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, STD PCR, vers. 2

Helpful Links

Optimizing PCR Protocols

References

References

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]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection. 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
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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In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

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.