Overview

Also Known As:testicular feminization

The androgen receptor; testicular feminization (Ar^Tfm) allele in this strain is a dominant, spontaneous mutation on the X chromosome that results in abnormal development of reproductive organs and tissues in males.

Genetic overview

Genetic Background	Generation
000664 C57BL/6J

A^w-J

Allele Type	Gene Symbol	Gene Name
Spontaneous	a	nonagouti

Eda^Ta-6J

Allele Type	Gene Symbol	Gene Name
Spontaneous	Eda	ectodysplasin-A

Ar^Tfm

Allele Type	Gene Symbol	Gene Name
Spontaneous	Ar	androgen receptor

View Genetics

Research Applications

Developmental Biology Research
Sensorineural Research
Mouse/Human Gene Homologs
Endocrine Deficiency Research
Reproductive Biology Research
Dermatology Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Testicular feminization (Ar^Tfm) is a dominant spontaneous mutation on the X chromosome. Hemizygous male mice are outwardly female in appearance except that the vagina does not open until 3 months of age if at all. Male reproductive development is abnormal leading to very small testes, and the absense of vas deferens, the epididymis, and male accessory glands. Spermatogonia and Sertoli cells are present in the testes, but spermatogenesis does not proceed past meiotic prophase. Leydig cells, which normally produce androgen in males, fail to develop normally. This strain is also segregating for the tabby 6J mutation (Eda^Ta-6J) that affects both the coat color and hair pattern growth. The tabby mutation is maintained in repulsion with the testicular feminization mutation and is used as a coat color marker to assist in identifying resulting genotypes obtained from matings.

Development

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 2 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.

Control Suggestions

Approximate Controls

000051 C57BL/6J-A^w-J/J

Additional Information

Considerations for Choosing Controls

Selected References

Charest NJ; Zhou ZX; Lubahn DB; Olsen KL; Wilson EM; French FS. 1991. A frameshift mutation destabilizes androgen receptor messenger RNA in the Tfm mouse. Mol Endocrinol 5(4):573-81PubMed: 1681426 MGI: J:712
Dulos GJ; Bagchus WM. 2001. Androgens indirectly accelerate thymocyte apoptosis. Int Immunopharmacol 1(2):321-8PubMed: 11360932 MGI: J:109877
Gaspar ML; Bourgarel P; Meo T; Tosi M. 1991. [Structure of messenger RNA of androgen receptor in mice and molecular characterization in Tfm mutant] C R Seances Soc Biol Fil 185(6):510-9PubMed: 1822400 MGI: J:1264
Gaspar ML; Meo T; Bourgarel P; Guenet JL; Tosi M. 1991. A single base deletion in the Tfm androgen receptor gene creates a short-lived messenger RNA that directs internal translation initiation. Proc Natl Acad Sci U S A 88(19):8606-10PubMed: 1924321 MGI: J:30797
Johnston DS; Russell LD; Friel PJ; Griswold MD. 2001. Murine germ cells do not require functional androgen receptors to complete spermatogenesis following spermatogonial stem cell transplantation. Endocrinology 142(6):2405-8PubMed: 11356688 MGI: J:109878
Kurita T; Wang YZ; Donjacour AA; Zhao C; Lydon JP; O'Malley BW; Isaacs JT; Dahiya R; Cunha GR. 2001. Paracrine regulation of apoptosis by steroid hormones in the male and female reproductive system. Cell Death Differ 8(2):192-200PubMed: 11313721 MGI: J:109881
Li-Hawkins J; Lund EG; Turley SD; Russell DW. 2000. Disruption of the oxysterol 7alpha-hydroxylase gene in mice. J Biol Chem 275(22):16536-42PubMed: 10748048 MGI: J:62587
Lyon MF; Hawkes SG. 1970. X-linked gene for testicular feminization in the mouse. Nature 227(5264):1217-9PubMed: 5452809 MGI: J:5173
Murphy L; Jeffcoate IA; O'Shaughnessy PJ. 1994. Abnormal Leydig cell development at puberty in the androgen-resistant Tfm mouse. Endocrinology 135(4):1372-7PubMed: 7925099 MGI: J:20980

View All References

Genetics

A^w-J

Allele Symbol: A^w-J

Allele Name	white bellied agouti Jackson
Allele Type	Spontaneous
Allele Synonym(s)	A^WJ
Gene Symbol and Name	a, nonagouti
Gene Synonym(s)
Strain of Origin	C57BL/6J
Chromosome	2

Eda^Ta-6J

Allele Symbol: Eda^Ta-6J

Allele Name	tabby 6 Jackson
Allele Type	Spontaneous
Allele Synonym(s)	Ta^6J; Ta2; Tabby
Gene Symbol and Name	Eda, ectodysplasin-A
Gene Synonym(s)
Strain of Origin	C57BL/6J-tp^3J/J
Chromosome	X
Molecular Note	This allele is defined by a base pair deletion (at position 1049) resulting in a frameshift mutation.

Ar^Tfm

Allele Symbol: Ar^Tfm

Allele Name	testicular feminization
Allele Type	Spontaneous
Allele Synonym(s)	Tfm
Gene Symbol and Name	Ar, androgen receptor
Gene Synonym(s)
Strain of Origin	(STOCK Eda^Ta x Atp7a^Mo-blo)F1
Chromosome	X
General Note	Ar^Tfm acts by causing insensitivity to androgens due to a defect in androgen-binding receptor present in cytosol and nucleus. Most responses to androgens are absent or defective in Ar^Tfm/Y males and are not inducible by administration of androgens (J:5221, J:5532). Androgen receptor is found in kidney, submandibular gland (J:5667) and brain (J:5927). Ar^Tfm/Y males have about 20-25 percent of normal testosterone-binding activity in brain (J:6096) and 10-20 percent in kidney.
Molecular Note	A frameshift mutation resulting from the deletion of a single cytosine residue generated a premature stop codon at residue 412. The nonsense mutation is expected to preclude the translation of both the DNA- and steroid-binding domains.

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

androgen insensitivity syndrome

Research Areas By Phenotype

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

Genotype: Eda^Ta-6J related

Developmental Biology Research
- Eye Defects
Sensorineural Research
- Eye Defects
Mouse/Human Gene Homologs
- hypohidrotic ectodermal dysplasia
Dermatology Research
- Color and White Spotting Defects
- Skin and Hair Texture Defects

Genotype: Ar^Tfm related

Endocrine Deficiency Research
- Gonad Defects
Reproductive Biology Research
- Developmental Defects Affecting Gonads
- Fertility Defects
Mouse/Human Gene Homologs
- testicular feminization

Mammalian Phenotype Terms by Genotype

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

Genotype: Ar^Tfm/Y
involves: NMRI * STOCK Eda Atp7a

reproductive system phenotype

secondary sex reversal
- male mice have female genitals, a blind ending vagina, inguinal testes, no scrotum and lack derivatives of the Wolffian ducts

increased testis tumor incidence
- Background Sensitivity - 4 of 46 mice exhibit unilateral Leydig tumor unlike Ar^Tfm male mice on the original stock background
- Normal - however, no germ cell tumors are observed

abnormal seminiferous tubule morphology
- Background Sensitivity - mice exhibit greater thickening and hyperplasia of peritubular myoid cells compared to Ar^Tfm male mice on the original stock background

enlarged seminiferous tubules
- Background Sensitivity - in 15 of 46 mice unlike Ar^Tfm male mice on the original stock background

arrest of male meiosis
- spermatogenesis does not proceed beyond meiosis prophase

cryptorchism

increased Leydig cell number
- Background Sensitivity - unlike Ar^Tfm male mice on the original stock background

endocrine/exocrine gland phenotype

increased Leydig cell number
- Background Sensitivity - unlike Ar^Tfm male mice on the original stock background

enlarged seminiferous tubules
- Background Sensitivity - in 15 of 46 mice unlike Ar^Tfm male mice on the original stock background

increased testis tumor incidence
- Normal - however, no germ cell tumors are observed
- Background Sensitivity - 4 of 46 mice exhibit unilateral Leydig tumor unlike Ar^Tfm male mice on the original stock background

cryptorchism

abnormal seminiferous tubule morphology
- Background Sensitivity - mice exhibit greater thickening and hyperplasia of peritubular myoid cells compared to Ar^Tfm male mice on the original stock background

neoplasm

increased testis tumor incidence
- Normal - however, no germ cell tumors are observed
- Background Sensitivity - 4 of 46 mice exhibit unilateral Leydig tumor unlike Ar^Tfm male mice on the original stock background

Genotype: Ar^Tfm/Y
Not Specified

reproductive system phenotype

abnormal testis morphology
- an extra layer of parietal lymphatic cells was present, but these cells appeared to be normal; myoid cells were also normal
- i?id=MGI:1934259"> Dhh^tm1Amc feminized males
- collagen and basal lamina material between Sertoli and myoid cells extended around the entire seminiferous tubule unlike that of the patchy basal lamina seen in Dhh^tm1Amc feminized males
- zed males
- peritubular fibrosis was observed, as indicated by a few extra layers of fibroblastic-like cells around the seminiferous tubules, although this fibrosis was not as severe as that seen in Dhh^tm1Amc feminized males

abnormal spermatogenesis
- germ cell development progressed to spermatocytes

abnormal adult Leydig cell differentiation
- at 63 days of age, testes from adult male hemizygotes contained abundant adult-type Leydig cells which appeared relatively undifferentiated and lacked smooth endoplasmic reticulum

endocrine/exocrine gland phenotype

abnormal testis morphology
- zed males
- peritubular fibrosis was observed, as indicated by a few extra layers of fibroblastic-like cells around the seminiferous tubules, although this fibrosis was not as severe as that seen in Dhh^tm1Amc feminized males
- an extra layer of parietal lymphatic cells was present, but these cells appeared to be normal; myoid cells were also normal
- collagen and basal lamina material between Sertoli and myoid cells extended around the entire seminiferous tubule unlike that of the patchy basal lamina seen in Dhh^tm1Amc feminized males
- i?id=MGI:1934259"> Dhh^tm1Amc feminized males

abnormal adult Leydig cell differentiation
- at 63 days of age, testes from adult male hemizygotes contained abundant adult-type Leydig cells which appeared relatively undifferentiated and lacked smooth endoplasmic reticulum

nervous system phenotype

abnormal sensory neuron innervation pattern
- mammary glands of male mice are innervated as in female mice

References

Charest NJ; Zhou ZX; Lubahn DB; Olsen KL; Wilson EM; French FS. 1991. A frameshift mutation destabilizes androgen receptor messenger RNA in the Tfm mouse. Mol Endocrinol 5(4):573-81PubMed: 1681426 MGI: J:712
Dulos GJ; Bagchus WM. 2001. Androgens indirectly accelerate thymocyte apoptosis. Int Immunopharmacol 1(2):321-8PubMed: 11360932 MGI: J:109877
Gaspar ML; Bourgarel P; Meo T; Tosi M. 1991. [Structure of messenger RNA of androgen receptor in mice and molecular characterization in Tfm mutant] C R Seances Soc Biol Fil 185(6):510-9PubMed: 1822400 MGI: J:1264
Gaspar ML; Meo T; Bourgarel P; Guenet JL; Tosi M. 1991. A single base deletion in the Tfm androgen receptor gene creates a short-lived messenger RNA that directs internal translation initiation. Proc Natl Acad Sci U S A 88(19):8606-10PubMed: 1924321 MGI: J:30797
Johnston DS; Russell LD; Friel PJ; Griswold MD. 2001. Murine germ cells do not require functional androgen receptors to complete spermatogenesis following spermatogonial stem cell transplantation. Endocrinology 142(6):2405-8PubMed: 11356688 MGI: J:109878
Kurita T; Wang YZ; Donjacour AA; Zhao C; Lydon JP; O'Malley BW; Isaacs JT; Dahiya R; Cunha GR. 2001. Paracrine regulation of apoptosis by steroid hormones in the male and female reproductive system. Cell Death Differ 8(2):192-200PubMed: 11313721 MGI: J:109881
Li-Hawkins J; Lund EG; Turley SD; Russell DW. 2000. Disruption of the oxysterol 7alpha-hydroxylase gene in mice. J Biol Chem 275(22):16536-42PubMed: 10748048 MGI: J:62587
Lyon MF; Hawkes SG. 1970. X-linked gene for testicular feminization in the mouse. Nature 227(5264):1217-9PubMed: 5452809 MGI: J:5173
Murphy L; Jeffcoate IA; O'Shaughnessy PJ. 1994. Abnormal Leydig cell development at puberty in the androgen-resistant Tfm mouse. Endocrinology 135(4):1372-7PubMed: 7925099 MGI: J:20980

Additional References

Tullis KM; Krebs CJ; Leung JY; Robins DM. 2003. The regulator of sex-limitation gene, rsl, enforces male-specific liver gene expression by negative regulation. Endocrinology 144(5):1854-60PubMed: 12697692 MGI: J:83502

Additional - A^w-J related

Additional - Ar^Tfm related

Additional - Eda^Ta-6J related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Restriction Enzyme Digest:Ar
- Sanger sequencing:Ar-SEQ
- Separated PCR:A A A Alternate2
- Genotyping resources and troubleshooting
Appearance
- white-bellied agouti, males with female external genitalia (no vaginal opening)
  Related Genotype: A^w-J/A^w-J + Ar^Tfm/Y males
  
  tabby (yellow coat, no hair on ears and tail, bald patch behind ears, no guard hairs)
  Related Genotype: A^w-J/A^w-J Eda^Ta-6J +/Y males
  
  white bellied agouti with mosaic striped coat
  Related Genotype: A^w-J/A^w-J Eda^Ta-6J +/+ Ar^Tfm females
  
  tabby (yellow coat, no hair on ears and tail, bald patch behind ears; no guard hairs)
  Related Genotype: A^w-J/A^w-J Eda^Ta-6J +/Eda^Ta-6J + females
Citation
When using the testicular feminization mouse strain in a publication, please cite the originating article(s) and include JAX stock #001809 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

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

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	X linked - Compound Heterozygous females for Eda<Ta-6J> and Ar<Tfm>, Hemizyous males for Eda<Ta-6J>, 1 pair minimum

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:testicular feminization

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Aw-J

Allele Symbol: Aw-J

EdaTa-6J

Allele Symbol: EdaTa-6J

ArTfm

Allele Symbol: ArTfm

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Research Areas By Phenotype

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

Genotype: EdaTa-6J related

Genotype: ArTfm related

Mammalian Phenotype Terms by Genotype

Genotype: ArTfm/Yinvolves: NMRI * STOCK Eda Atp7a

reproductive system phenotype

endocrine/exocrine gland phenotype

neoplasm

Genotype: ArTfm/YNot Specified

reproductive system phenotype

endocrine/exocrine gland phenotype

nervous system phenotype

References

Additional References

Additional - Aw-J related

Additional - ArTfm related

Additional - EdaTa-6J related

Genotyping Protocols

Appearance

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

A^w-J

Allele Symbol: A^w-J

Eda^Ta-6J

Allele Symbol: Eda^Ta-6J

Ar^Tfm

Allele Symbol: Ar^Tfm

Genotype: Eda^Ta-6J related

Genotype: Ar^Tfm related

Genotype: Ar^Tfm/Y
involves: NMRI * STOCK Eda Atp7a

Genotype: Ar^Tfm/Y
Not Specified

Additional - A^w-J related

Additional - Ar^Tfm related

Additional - Eda^Ta-6J related