Description

Strain Information

Type Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation N?+2   Donating Investigator Rudolf Jaenisch,   Massachusetts Institute of Technology

Description
Homozygous mice are deficient in activin B (betaB:betaB), activin AB (betaA:betaB) and inhibin B (alpha:betaB). Heterozygotes appear normal. Homozygous mutants complete embryonic development and are viable. They are born, however, with open eyes which leads to the development of eye lesions. Homozygous males breed normally but mutant females exhibit a profoundly impaired reproductive ability, characterized by perinatal lethality of their offspring. Mutant females have an increased gestation time and decreased nursing ability that may be the result of impaired milk let-down. There is an upregulation of beta-A activin which may contribute to the phenotype.

Control Information

	Control
	Wild-type from the colony
	002448 129S1/SvImJ	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying   Inhbb^tm1Jae allele

002442	B6.129S4-Inhbbtm1Jae/J
002368	C.129S4(B6)-Inhbbtm1Jae/J

View Strains carrying   Inhbb^tm1Jae     (2 strains)

Additional Web Information

New 129 Nomenclature Bulletin

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Inhbb^tm1Jae/Inhbb^tm1Jae

        either: (129S4/SvJae-Inhbb^tm1Jae) or (involves: 129S4/SvJae * BALB/c) or (involves: 129S4/SvJae * C57BL/6)

• lethality-postnatal
• postnatal lethality (MGI Ref ID J:16995)
  • at weaning fewer than expected mice survive on a 129S4/SvJae BALB/c background compared to on a 124S4/SvJae C57BL/6 background with both exhibiting decreased survival relative to wild-type mice
• life span-post-weaning/aging
• pregnancy-related premature death (MGI Ref ID J:16995)
  • in some females initiation of labor fails resulting in the death of the female and fetuses in utero
• reproductive system phenotype
• abnormal mammary gland morphology (MGI Ref ID J:16995)
  • at 0.5 days after delivery there is an increase in the glandular to adipose tissue ratio and vacuolation of the lobules of the mammary gland is observed
• abnormal milk ejection (MGI Ref ID J:16995)
  • maternally dependent fetal death is associated with a failure of milk to be ejected as pups fostered by wild-type mice survive
  • milk accumulates in the mammary tissue at day 0.5 after delivery
• long gestation period (MGI Ref ID J:16995)
  • most females deliver on E20.5 and some on E21.5 instead of E19.5 as wild-type females do
• reduced female fertility (MGI Ref ID J:16995)
  • female mice have a reduced ability to produce live offspring regardless of genotype to which they are mated
  • female mice give birth to normal sized litters that die within the first day after birth regardless of genotype
  • female mice with the 129S4/SvJae BALB/c background are most severely affected
• vision/eye phenotype
• abnormal eye morphology (MGI Ref ID J:16995)
  • ocular dystrophy is observed in mice whose eyelids were delayed in opening
• abnormal corneal epithelium morphology (MGI Ref ID J:16995)
  • hyperkeratinization and squamous metaplasia of the corneal epithelium is observed during the first day after birth in mice with open eyelids
• corneal opacity (MGI Ref ID J:16995)
  • corneal opacification is observed in mice whose eyelids were delayed in opening
• delayed eyelid opening (MGI Ref ID J:16995)
  • eyelids that were open at birth and subsequently resealed exhibit a delay in reopening
• eyelids open at birth (MGI Ref ID J:16995)
  • some mice have open eye lids at birth but seal in subsequent days
  • fewer mice on the 129S4/SvJae BALB/c background had open eyelids at birth compared to on the 129S4/SvJae C57BL/6 background and no mice on an inbred 129S4/SvJae background had open eyelids at birth
• increased incidence of corneal inflammation (MGI Ref ID J:16995)
  • increased inflammation of the cornea and eyelids is observed on the first day after birth in mice with open eyelids
• homeostasis/metabolism phenotype
• increased circulating follicle stimulating hormone level (MGI Ref ID J:16995)
  • serum follicle stimulating hormone levels are increased by about 20% relative to in heterozygotes
• endocrine/exocrine gland phenotype
• abnormal mammary gland morphology (MGI Ref ID J:16995)
  • at 0.5 days after delivery there is an increase in the glandular to adipose tissue ratio and vacuolation of the lobules of the mammary gland is observed
• abnormal milk ejection (MGI Ref ID J:16995)
  • maternally dependent fetal death is associated with a failure of milk to be ejected as pups fostered by wild-type mice survive
  • milk accumulates in the mammary tissue at day 0.5 after delivery
• immune system phenotype
• increased incidence of corneal inflammation (MGI Ref ID J:16995)
  • increased inflammation of the cornea and eyelids is observed on the first day after birth in mice with open eyelids

View Research Applications

Research Applications

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

Inhbb^tm1Jae related

Cancer Research
Genes Regulating Growth and Proliferation

Developmental Biology Research
Eye Defects

Reproductive Biology Research
Developmental Defects Affecting Gonads (females only)
Fertility Defects

Sensorineural Research
Eye Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Inhbbtm1Jae
Allele Name		targeted mutation 1, Rudolf Jaenisch
Allele Type		Targeted (knock-out)
Common Name(s)		Inhbb-; bb1; bb2;
Mutation Made By		Rudolf Jaenisch,   Massachusetts Institute of Technology
Strain of Origin		129S4/SvJae
ES Cell Line Name		J1
ES Cell Line Strain		129S4/SvJae
Gene Symbol and Name		Inhbb, inhibin beta-B
Chromosome		1
Gene Common Name(s)		MGC157939; activin;
Molecular Note		A neomycin resistance cassette replaced a 1.3 kb region of the gene, which spanned the translational start codon, the signal peptide coding region, and most of exon 1 of the gene. In the construct designated bb1, the neomycin cassette was inserted in the same transcriptional orientation as the gene; in the construct designated bb2, the neomycin cassette was inserted in the reverse orientation. [MGI Ref ID J:16995]

Genotyping

Genotyping Information

Genotyping Protocols

Inhbb^tm1Jae, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Vassalli A; Matzuk MM; Gardner HA; Lee KF; Jaenisch R. 1994. Activin/inhibin beta B subunit gene disruption leads to defects in eyelid development and female reproduction. Genes Dev 8(4):414-27. [PubMed: 8125256]  [MGI Ref ID J:16995]

Additional References

Inhbb^tm1Jae related

Bertolino P; Holmberg R; Reissmann E; Andersson O; Berggren PO; Ibanez CF. 2008. Activin B receptor ALK7 is a negative regulator of pancreatic beta-cell function. Proc Natl Acad Sci U S A 105(20):7246-51. [PubMed: 18480258]  [MGI Ref ID J:136342]

Brown CW; Houston-Hawkins DE; Woodruff TK; Matzuk MM. 2000. Insertion of Inhbb into the Inhba locus rescues the Inhba-null phenotype and reveals new activin functions. Nat Genet 25(4):453-7. [PubMed: 10932194]  [MGI Ref ID J:63882]

Brown CW; Li L; Houston-Hawkins DE; Matzuk MM. 2003. Activins are critical modulators of growth and survival. Mol Endocrinol 17(12):2404-17. [PubMed: 14551263]  [MGI Ref ID J:86858]

Ferguson CA; Tucker AS; Christensen L; Lau AL; Matzuk MM; Sharpe PT. 1998. Activin is an essential early mesenchymal signal in tooth development that is required for patterning of the murine dentition. Genes Dev 12(16):2636-49. [PubMed: 9716414]  [MGI Ref ID J:49552]

Li Q; Karam SM; Coerver KA; Matzuk MM; Gordon JI. 1998. Stimulation of activin receptor II signaling pathways inhibits differentiation of multiple gastric epithelial lineages. Mol Endocrinol 12(2):181-92. [PubMed: 9482661]  [MGI Ref ID J:110642]

Matzuk MM; Kumar TR; Vassalli A; Bickenbach JR; Roop DR; Jaenisch R; Bradley A. 1995. Functional analysis of activins during mammalian development [see comments] Nature 374(6520):354-6. [PubMed: 7885473]  [MGI Ref ID J:23923]

Pangas SA; Jorgez CJ; Tran M; Agno J; Li X; Brown CW; Kumar TR; Matzuk MM. 2007. Intraovarian activins are required for female fertility. Mol Endocrinol 21(10):2458-71. [PubMed: 17609433]  [MGI Ref ID J:125354]

Robinson GW; Hennighausen L. 1997. Inhibins and activins regulate mammary epithelial cell differentiation through mesenchymal-epithelial interactions. Development 124(14):2701-8. [PubMed: 9226441]  [MGI Ref ID J:41813]

Shillingford JM; Miyoshi K; Robinson GW; Bierie B; Cao Y; Karin M; Hennighausen L. 2003. Proteotyping of mammary tissue from transgenic and gene knockout mice with immunohistochemical markers: a tool to define developmental lesions. J Histochem Cytochem 51(5):555-65. [PubMed: 12704203]  [MGI Ref ID J:124525]

Simmons DG; Cross JC. 2005. Determinants of trophoblast lineage and cell subtype specification in the mouse placenta. Dev Biol 284(1):12-24. [PubMed: 15963972]  [MGI Ref ID J:100602]

Yao HH; Aardema J; Holthusen K. 2006. Sexually dimorphic regulation of inhibin Beta B in establishing gonadal vasculature in mice. Biol Reprod 74(5):978-83. [PubMed: 16452457]  [MGI Ref ID J:107812]

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
	002448 129S1/SvImJ	(approximate)
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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Contact Information
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Fax: 207.288.6150
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Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
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Contact information

General inquiries

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

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