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. Visit our online Nomenclature tutorial. Species laboratory mouse   Donating Investigator Dr. Sally A. Camper,   University of Michigan Medical School

Appearance
black
Related Genotype: a/a

Description
Mice homozygous for the Cga^tm1Sac targeted mutation are viable but both sexes are infertile. They lack TSH, LH, and FSH. Homozygous mutant mice are hypogonadal and exhibit severe hypothyroidism resulting in dwarfism. Development of the thyroid gland was arrested in late gestation. However, gonadotropin releasing hormone (GNRH) neuron migration, development of secondary sex organs, and fetal and neonatal gonadal development are normal. Mice heterozygous for the Cga^tm1Sac targeted mutation appear normal.

Control Information

	Control
	Wild-type from the colony
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Cga

004426

B6;SJL-Tg(Cga-cre)3Sac/J

View Strains carrying other alleles of Cga     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Cga^tm1Sac/Cga^tm1Sac

        involves: 129S2/SvPas * C57BL/6J

• endocrine/exocrine gland phenotype
• *normal* endocrine/exocrine gland phenotype
  • normal gonadotrope cellularity   (MGI Ref ID J:28450)
• • abnormal corpus luteum morphology   (MGI Ref ID J:28450)
  • abnormal thyroid follicle morphology
    • disorganized follicles   (MGI Ref ID J:28450)
  • absent mature ovarian follicles   (MGI Ref ID J:28450)
  • decreased activity of thyroid
    • hypothyroid   (MGI Ref ID J:28450)
  • decreased lactotroph cell number
    • lactotropes are reduced in number in females   (MGI Ref ID J:28450)
  • • absent lactotrophs
      • lactotropes were undetected in males   (MGI Ref ID J:28450)
  • decreased somatotroph cell number
    • reduced somatotrope cellularity   (MGI Ref ID J:28450)
  • impaired ovarian folliculogenesis
    • follicles were reduced in size   (MGI Ref ID J:28450)
    • no progress beyond the preantral stage   (MGI Ref ID J:28450)
  • increased thyrotroph cell number
    • thyotrope hyperplasia and hypertrophy   (MGI Ref ID J:28450)
  • small ovary   (MGI Ref ID J:28450)
  • small seminal vesicle
    • seminal glands were not readily visible, consistent with testosterone deficiency   (MGI Ref ID J:28450)
  • small seminiferous tubules
    • development of the tubules ceased perinatally   (MGI Ref ID J:28450)
  • small testis
    • size reduction observed at 8 weeks of age   (MGI Ref ID J:28450)
• growth/size phenotype
• decreased body size
  • mice were approximately half the size of wild-type littermates at 4.5 weeks of age   (MGI Ref ID J:28450)
• • decreased body weight
    • first evident between 2 and 3 weeks of age   (MGI Ref ID J:28450)
  • proportional dwarf   (MGI Ref ID J:28450)
• postnatal growth retardation
  • no gender difference in size, putatively due to the decrease in testosterone levels   (MGI Ref ID J:28450)
• homeostasis/metabolism phenotype
• decreased circulating follicle stimulating hormone level   (MGI Ref ID J:28450)
• decreased circulating luteinizing hormone level   (MGI Ref ID J:28450)
• decreased circulating testosterone level
  • serum testosterone was undetected in male mice   (MGI Ref ID J:28450)
• decreased circulating thyroid-stimulating hormone level   (MGI Ref ID J:28450)
• reproductive system phenotype
• abnormal corpus luteum morphology   (MGI Ref ID J:28450)
• abnormal ovulation   (MGI Ref ID J:28450)
• absent mature ovarian follicles   (MGI Ref ID J:28450)
• arrest of male meiosis
  • spermatogenesis was blocked at meiosis I   (MGI Ref ID J:28450)
• female infertility   (MGI Ref ID J:28450)
• impaired ovarian folliculogenesis
  • follicles were reduced in size   (MGI Ref ID J:28450)
  • no progress beyond the preantral stage   (MGI Ref ID J:28450)
• male infertility   (MGI Ref ID J:28450)
• small ovary   (MGI Ref ID J:28450)
• small seminal vesicle
  • seminal glands were not readily visible, consistent with testosterone deficiency   (MGI Ref ID J:28450)
• small seminiferous tubules
  • development of the tubules ceased perinatally   (MGI Ref ID J:28450)
• small testis
  • size reduction observed at 8 weeks of age   (MGI Ref ID J:28450)
• uterus hypoplasia
  • underdeveloped and threadlike at 3 weeks of age   (MGI Ref ID J:28450)
• vagina atresia   (MGI Ref ID J:28450)
• nervous system phenotype
• decreased lactotroph cell number
  • lactotropes are reduced in number in females   (MGI Ref ID J:28450)
• • absent lactotrophs
    • lactotropes were undetected in males   (MGI Ref ID J:28450)
• decreased somatotroph cell number
  • reduced somatotrope cellularity   (MGI Ref ID J:28450)
• increased thyrotroph cell number
  • thyotrope hyperplasia and hypertrophy   (MGI Ref ID J:28450)

View Research Applications

Research Applications

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

Cga^tm1Sac related

Developmental Biology Research
Growth Defects
Internal/Organ Defects
      gonad, thyroid

Endocrine Deficiency Research
Gonad Defects
Hypothalamus/Pituitary Defects
Thyroid Defects

Internal/Organ Research
Thyroid Defects

Reproductive Biology Research
Developmental Defects Affecting Gonads
Endocrine Deficiencies Affecting Gonads
Fertility Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Cgatm1Sac
Allele Name		targeted mutation 1, Sally A Camper
Allele Type		Targeted (knock-out)
Common Name(s)		TSHalpha -;
Mutation Made By		Dr. Sally Camper,   University of Michigan Medical School
Strain of Origin		129S2/SvPas
ES Cell Line Name		D3
ES Cell Line Strain		129S2/SvPas
Gene Symbol and Name		Cga, glycoprotein hormones, alpha subunit
Chromosome		4
Gene Common Name(s)		CG-ALPHA; FSHA; GPHA1; GPHa; GPHalpha; HCG; LHA; TSHA; Tsha; aGSU; alpha-GSU; alphaGSU; alphaSU; thyrotropin stimulating hormone, alpha subunit;
Molecular Note		A neomycin resistance gene was inserted into the third exon. In situ hybridization and RT-PCR experiments confirmed that the transcript was not present in pituitary of homozygous mice (data not shown). [MGI Ref ID J:28450]

Genotyping

Genotyping Information

Genotyping Protocols

Cga^tm1Sac, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Kendall SK; Samuelson LC; Saunders TL; Wood RI; Camper SA. 1995. Targeted disruption of the pituitary glycoprotein hormone alpha-subunit produces hypogonadal and hypothyroid mice. Genes Dev 9(16):2007-19. [PubMed: 7544315]  [MGI Ref ID J:28450]

Additional References

Brinkmeier ML; Stahl JH; Gordon DF; Ross BD; Sarapura VD; Dowding JM; Kendall SK; Lloyd RV; Ridgway EC; Camper SA. 2001. Thyroid hormone-responsive pituitary hyperplasia independent of somatostatin receptor 2. Mol Endocrinol 15(12):2129-36. [PubMed: 11731614]  [MGI Ref ID J:72988]

Cga^tm1Sac related

Brinkmeier ML; Stahl JH; Gordon DF; Ross BD; Sarapura VD; Dowding JM; Kendall SK; Lloyd RV; Ridgway EC; Camper SA. 2001. Thyroid hormone-responsive pituitary hyperplasia independent of somatostatin receptor 2. Mol Endocrinol 15(12):2129-36. [PubMed: 11731614]  [MGI Ref ID J:72988]

Choi Y; Rajkovic A. 2006. Genetics of early mammalian folliculogenesis. Cell Mol Life Sci 63(5):579-90. [PubMed: 16416028]  [MGI Ref ID J:108336]

Karolyi IJ; Dootz GA; Halsey K; Beyer L; Probst FJ; Johnson KR; Parlow AF; Raphael Y; Dolan DF; Camper SA. 2007. Dietary thyroid hormone replacement ameliorates hearing deficits in hypothyroid mice. Mamm Genome 18(8):596-608. [PubMed: 17899304]  [MGI Ref ID J:125708]

Kulig E; Camper SA; Kuecker S; Jin L; Lloyd RV. 1998. Remodeling of hyperplastic pituitaries in hypothyroid alpha-subunit knockout mice after thyroxine and 17 beta- estradiol treatment: Role of apoptosis. Endocr Pathol 9(3):261-274. [PubMed: 12114718]  [MGI Ref ID J:51465]

Lloyd RV; Ruebel KH; Zhang S; Jin L. 2002. Pituitary Hyperplasia in Glycoprotein Hormone Alpha Subunit-, p18(INK4C)-, and p27(kip-1)-Null Mice : Analysis of Proteins Influencing p27(kip-1) Ubiquitin Degradation. Am J Pathol 160(3):1171-9. [PubMed: 11891212]  [MGI Ref ID J:75216]

Stahl JH; Kendall SK; Brinkmeier ML; Greco TL; Watkins-Chow DE; Campos-Barros A; Lloyd RV; Camper SA. 1999. Thyroid hormone is essential for pituitary somatotropes and lactotropes. Endocrinology 140(4):1884-92. [PubMed: 10098528]  [MGI Ref ID J:108821]

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
	101045 B6129SF2/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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