Strain Name:

B6;129S4-Lhx3tm1Lmgd/J

Stock Number:

007675

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Cryopreserved - Ready for recovery

Mice homozygous for this targeted mutation exhibit abnormal pituitary development with the posterior lobe forming normally and the anterior and intermediate lobes failing to form. This mutant mouse strain may be useful in studies of pituitary development.

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 Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Specieslaboratory mouse
 
Donating InvestigatorDr. Heiner Westphal,   National Institutes of Health

Description
Mice heterozygous for this targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Homozygous mice have a perinatal phenotype and are stillborn or die within 24 hours of birth. Embryos homozygous for the mutation do not exhibit the gene product (mRNA) as detected by in situ hybridization. Homozygotes exhibit abnormal pituitary development with the posterior lobe forming normally and the anterior and intermediate lobes failing to form. Although development of Rathke’s pouch, the precursor of the anterior and intermediate lobes of the pituitary, is initially normal, by embryonic day 12.5 homozygotes exhibit marked hypoplasia and growth arrest. This mutant mouse strain may be useful in studies of pituitary development.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt the sequence encoding the two LM domains and some of the homeodomain. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were used to produce chimeric animals by injection into recipient blastocysts or by aggregation. The resulting chimeric animals were crossed to C57BL/6 mice to generate the colony. Lhx3-mutant mice were then maintained on this mixed C57BL/6;129S4 genetic background prior to sending to The Jackson Laboratory Repository. Upon arrival, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

Control Information

  Control
   101043 B6129SF1/J (approximate)
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Lhx3
018997   B6.129S(FVB)-Lhx3tm1.1Sjr/J
View Strains carrying other alleles of Lhx3     (1 strain)

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.
Pituitary Hormone Deficiency, Combined, 3; CPHD3   (LHX3)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Lhx3tm1Lmgd/Lhx3tm1Lmgd

        involves: 129S4/SvJae
  • mortality/aging
  • complete prenatal lethality
    • homozygotes are still born or die within the first 24 hours after birth   (MGI Ref ID J:33050)
    • those born alive are able to breath and so no obvious cause for death   (MGI Ref ID J:33050)
  • endocrine/exocrine gland phenotype
  • abnormal pituitary gland morphology
    • posterior lobe is normal   (MGI Ref ID J:33050)
    • abnormal adenohypophysis morphology   (MGI Ref ID J:33050)
      • abnormal corticotroph morphology
        • corticotroph cell lineage present but fails to proliferate   (MGI Ref ID J:33050)
      • absent adenohypophysis   (MGI Ref ID J:51420)
      • absent lactotrophs   (MGI Ref ID J:33050)
      • absent somatotrophs
        • anterior pituitary expression of GH was absent at E16.5, indicating an absence of somatotrophs   (MGI Ref ID J:33050)
      • absent thyrotrophs
        • anterior pituitary expression of TSHbeta was absent at E16.5, indicating an absence of thyrotrophs   (MGI Ref ID J:33050)
      • decreased gonadotroph cell number
        • no LH-expressing cells could be detected in the pituitary primordia at E18.5, suggesting an absence or at least a severely reduced number of gonadotrophs   (MGI Ref ID J:33050)
    • abnormal pituitary diverticulum morphology
      • Rathke's pouch is normal at E10.5 but failed to develop further   (MGI Ref ID J:33050)
    • absent pituitary intermediate lobe   (MGI Ref ID J:51420)
  • adrenal cortical hyperplasia   (MGI Ref ID J:33050)
  • nervous system phenotype
  • *normal* nervous system phenotype
    • motor neuron development is normal   (MGI Ref ID J:51420)
    • abnormal pituitary gland morphology
      • posterior lobe is normal   (MGI Ref ID J:33050)
      • abnormal adenohypophysis morphology   (MGI Ref ID J:33050)
        • abnormal corticotroph morphology
          • corticotroph cell lineage present but fails to proliferate   (MGI Ref ID J:33050)
        • absent adenohypophysis   (MGI Ref ID J:51420)
        • absent lactotrophs   (MGI Ref ID J:33050)
        • absent somatotrophs
          • anterior pituitary expression of GH was absent at E16.5, indicating an absence of somatotrophs   (MGI Ref ID J:33050)
        • absent thyrotrophs
          • anterior pituitary expression of TSHbeta was absent at E16.5, indicating an absence of thyrotrophs   (MGI Ref ID J:33050)
        • decreased gonadotroph cell number
          • no LH-expressing cells could be detected in the pituitary primordia at E18.5, suggesting an absence or at least a severely reduced number of gonadotrophs   (MGI Ref ID J:33050)
      • abnormal pituitary diverticulum morphology
        • Rathke's pouch is normal at E10.5 but failed to develop further   (MGI Ref ID J:33050)
      • absent pituitary intermediate lobe   (MGI Ref ID J:51420)
  • homeostasis/metabolism phenotype
  • decreased adrenocorticotropin level
    • in pitutitary   (MGI Ref ID J:33050)
  • decreased growth hormone level
    • not expressed in pituitary   (MGI Ref ID J:33050)
  • decreased luteinizing hormone level
    • no LH positive cells seen in pituitary   (MGI Ref ID J:33050)
  • decreased thyroid-stimulating hormone level
    • not expressed in pituitary   (MGI Ref ID J:33050)
View Research Applications

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

Endocrine Deficiency Research
Hypothalamus/Pituitary Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Lhx3tm1Lmgd
Allele Name targeted mutation 1, Laboratory of Mammalian Genes and Development, Heiner Westphal
Allele Type Targeted (Null/Knockout)
Common Name(s) Lhx3-;
Mutation Made ByDr. Heiner Westphal,   National Institutes of Health
Strain of Origin129S4/SvJae
ES Cell Line NameJ1
ES Cell Line Strain129S4/SvJae
Gene Symbol and Name Lhx3, LIM homeobox protein 3
Chromosome 2
Gene Common Name(s) CPHD3; LIM3; M2-LHX3; P-LIM; mLim-3;
Molecular Note Sequences encoding the two LIM domains and a portion of the homeodomain were replaced with a neomycin selection cassette. Transcript was undetected by in situ hybridization analysis of mutant embryos. [MGI Ref ID J:33050]

Genotyping

Genotyping Information


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Sheng HZ; Zhadanov AB; Mosinger B Jr; Fujii T; Bertuzzi S; Grinberg A; Lee EJ; Huang SP; Mahon KA; Westphal H. 1996. Specification of pituitary cell lineages by the LIM homeobox gene Lhx3. Science 272(5264):1004-7. [PubMed: 8638120]  [MGI Ref ID J:33050]

Additional References

Lhx3tm1Lmgd related

Ellsworth BS; Butts DL; Camper SA. 2008. Mechanisms underlying pituitary hypoplasia and failed cell specification in Lhx3-deficient mice. Dev Biol 313(1):118-29. [PubMed: 18037398]  [MGI Ref ID J:130185]

Ellsworth BS; Egashira N; Haller JL; Butts DL; Cocquet J; Clay CM; Osamura RY; Camper SA. 2006. FOXL2 in the pituitary: molecular, genetic, and developmental analysis. Mol Endocrinol 20(11):2796-805. [PubMed: 16840539]  [MGI Ref ID J:114716]

Hertzano R; Dror AA; Montcouquiol M; Ahmed ZM; Ellsworth B; Camper S; Friedman TB; Kelley MW; Avraham KB. 2007. Lhx3, a LIM domain transcription factor, is regulated by Pou4f3 in the auditory but not in the vestibular system. Eur J Neurosci 25(4):999-1005. [PubMed: 17331196]  [MGI Ref ID J:119779]

Metz H; Wray S. 2010. Use of mutant mouse lines to investigate origin of gonadotropin-releasing hormone-1 neurons: lineage independent of the adenohypophysis. Endocrinology 151(2):766-73. [PubMed: 20008041]  [MGI Ref ID J:168181]

Sharma K; Sheng HZ; Lettieri K; Li H; Karavanov A; Potter S; Westphal H; Pfaff SL. 1998. LIM homeodomain factors Lhx3 and Lhx4 assign subtype identities for motor neurons. Cell 95(6):817-28. [PubMed: 9865699]  [MGI Ref ID J:51420]

Sheng HZ; Moriyama K; Yamashita T; Li H; Potter SS; Mahon KA; Westphal H. 1997. Multistep control of pituitary organogenesis. Science 278(5344):1809-12. [PubMed: 9388186]  [MGI Ref ID J:44644]

Tian G; Singh U; Yu Y; Ellsworth BS; Hemberger M; Geyer R; Stewart MD; Behringer RR; Fundele R. 2008. Expression and function of the LIM homeobox containing genes Lhx3 and Lhx4 in the mouse placenta. Dev Dyn 237(5):1517-25. [PubMed: 18425848]  [MGI Ref ID J:134683]

Zhao Y; Morales DC; Hermesz E; Lee WK; Pfaff SL; Westphal H. 2006. Reduced expression of the LIM-homeobox gene Lhx3 impairs growth and differentiation of Rathke's pouch and increases cell apoptosis during mouse pituitary development. Mech Dev 123(8):605-13. [PubMed: 16859901]  [MGI Ref ID J:119270]

Health & husbandry

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.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, these mice are bred as heterozygotes. Homozygotes have a perinatal lethal phenotype and are stillborn or die within 24 hours of birth.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2525.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We willfulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3283.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We willfulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   101043 B6129SF1/J (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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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