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 Generation ?+F1pN1 Generation Definitions   Donating Investigator Tian Xu,   Yale University School of Medicine, HHMI

Description
Homozygous animals exhibit a lack of mammary gland development, infertility and growth retardation. Accompanying these defects are hyperplastic changes in the pituitary and decreased serum hormone levels. The reproductive hormone defects of homozygotes are reminiscent of isolated luteinizing hormone (LH)-hypogonadotropic hypogonadism and corpus luteum insufficiency in humans. Furthermore, Homozygous mice develop soft tissue sarcomas (some by 4-10 months of age) and ovarian stromal cell tumors (by 3 months of age) and are highly sensitive to carcinogenic treatments. Data demonstrates a role for this gene in mammalian tumorigenesis and specific endocrine dysfunction.

Development
A neomycin resistance cassette replaces sequences that correspond to human gene amino acids 756-1130. The targeting vector was electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells. This strain was maintained on a mixed C57BL/6 and 129 genetic background by the donating laboratory.

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Lats1^tm1Tx/Lats1^tm1Tx

        involves: 129S2/SvPas * C57BL/6J

• mortality/aging
• partial neonatal lethality
  • incomplete penetrance, many mutant pups (60/101) dead during first postnatal day   (MGI Ref ID J:52536)
• partial postnatal lethality
  • of mice that survive the neonatal period, only 8% survive to three weeks of age   (MGI Ref ID J:52536)
• growth/size phenotype
• decreased body weight
  • weight at birth was approximately 70% of normal   (MGI Ref ID J:52536)
  • of mice that survived, weight remained at 60 - 70% of controls   (MGI Ref ID J:52536)
• reproductive system phenotype
• abnormal female reproductive system morphology   (MGI Ref ID J:52536)
• • abnormal ovarian follicle morphology
    • less prominent formation of the follicular antrum   (MGI Ref ID J:52536)
    • fewer degenerative granulosa cells in the follicles   (MGI Ref ID J:52536)
  • • decreased mature ovarian follicle number
      • any follicles seen were primary or secondary   (MGI Ref ID J:52536)
    • impaired ovarian folliculogenesis
      • ovaries contained fewer follicles than age- and parity-matched controls   (MGI Ref ID J:52536)
  • absent corpus luteum
    • corpus luteum formation lacking   (MGI Ref ID J:52536)
• abnormal fertility/fecundity   (MGI Ref ID J:52536)
• • female infertility
    • incomplete penetrance; 60% of females are completely sterile   (MGI Ref ID J:52536)
  • reduced fertility
    • decreased fertility, both males and females   (MGI Ref ID J:52536)
• absent estrous cycle
  • females remained in continual metestrous, never cycling   (MGI Ref ID J:52536)
• homeostasis/metabolism phenotype
• decreased circulating growth hormone level
  • females had reduced serum concentrations   (MGI Ref ID J:52536)
• decreased circulating luteinizing hormone level
  • females had reduced serum concentrations   (MGI Ref ID J:52536)
• decreased circulating prolactin level
  • females had reduced serum concentrations   (MGI Ref ID J:52536)
• cardiovascular system phenotype
• internal hemorrhage
  • neonatal death was accompanied by evidence of internal hemorrhage into vital organs   (MGI Ref ID J:52536)
• tumorigenesis
• increased ovary tumor incidence
  • females developed ovarian stromal cell tumors by 3 months of age   (MGI Ref ID J:52536)
• sarcoma
  • 14.3% of females, aged 4 to 10 months, developed large soft-tissue sarcomas   (MGI Ref ID J:52536)
• endocrine/exocrine gland phenotype
• abnormal mammary gland development
  • decreased amount of breast epithelial tissue, with complete absence of nipple formation in some females   (MGI Ref ID J:52536)
  • mammary glands reduced to a fat pad devoid of ductular component   (MGI Ref ID J:52536)
• • absent nipple
    • complete absence of nipple formation in some females   (MGI Ref ID J:52536)
• abnormal ovarian follicle morphology
  • less prominent formation of the follicular antrum   (MGI Ref ID J:52536)
  • fewer degenerative granulosa cells in the follicles   (MGI Ref ID J:52536)
• • decreased mature ovarian follicle number
    • any follicles seen were primary or secondary   (MGI Ref ID J:52536)
  • impaired ovarian folliculogenesis
    • ovaries contained fewer follicles than age- and parity-matched controls   (MGI Ref ID J:52536)
• absent corpus luteum
  • corpus luteum formation lacking   (MGI Ref ID J:52536)
• enlarged adenohypophysis
  • hyperplastic pituitaries, restricted to the anterior lobe   (MGI Ref ID J:52536)
• nervous system phenotype
• enlarged adenohypophysis
  • hyperplastic pituitaries, restricted to the anterior lobe   (MGI Ref ID J:52536)
• integument phenotype
• abnormal mammary gland development
  • decreased amount of breast epithelial tissue, with complete absence of nipple formation in some females   (MGI Ref ID J:52536)
  • mammary glands reduced to a fat pad devoid of ductular component   (MGI Ref ID J:52536)
• • absent nipple
    • complete absence of nipple formation in some females   (MGI Ref ID J:52536)

View Research Applications

Research Applications

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

Cancer Research
Increased Tumor Incidence
      Gonadal Tumors
      Gonadal Tumors: ovarian
      Other Tissues/Organs
Tumor Suppressor Genes

Developmental Biology Research
Embryonic Lethality (Homozygous)
      incomplete
Growth Defects
      Growth Defects (homozygous)

Endocrine Deficiency Research
Hypothalamus/Pituitary Defects
Mammary Gland Defects

Reproductive Biology Research
Endocrine Deficiencies Affecting Gonads
Fertility Defects
Gonadal Tumors
      ovarian

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Lats1tm1Tx
Allele Name		targeted mutation 1, Tian Xu
Allele Type		Targeted (knock-out)
Common Name(s)		Lats1-;
Mutation Made By		Tian Xu,   Yale University School of Medicine, HHMI
Strain of Origin		129S2/SvPas
ES Cell Line Name		D3
ES Cell Line Strain		129S2/SvPas
Gene Symbol and Name		Lats1, large tumor suppressor
Chromosome		10
Gene Common Name(s)		AW208599; RGD1564085; WARTS; expressed sequence AW208599; wts;
Molecular Note		A neomycin resistance cassette replaced sequence encoding amino acids 756 - 1130 of the protein. Immunoprecipitation and Western blots of embryonic fibroblasts lysates from homozygous mutant mice showed no detectable protein for the targeted gene. [MGI Ref ID J:52536]

Genotyping

Genotyping Information

Genotyping Protocols

Lats1^tm1Tx, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

St. John MA; Tao W; Fei X; Fukumoto R; Carcangiu ML; Brownstein DG; Parlow AF; McGrath J; Xu T. 1999. Mice deficient of Lats1 develop soft-tissue sarcomas, ovarian tumours and pituitary dysfunction. Nat Genet 21(2):182-6. [PubMed: 9988269]  [MGI Ref ID J:52536]

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 & Husbandry	When maintained as a live colony, heterozygotes may be bred. Recovery of homozygotes is reduced (approximately 5% from heterozygote x heterozygote crosses) as is postnatal survival. Homozygous males display decreased fertility and females display severe fertility defects.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	Wild-type from the colony
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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