B6.Cg-Tg(Sry)2Ei Sry^dl1Rlb/ArnoJ

Stock number: 010905
Strain synonyms: Tdy ml
Research areas: Developmental Biology Research, Reproductive Biology Research, Research Tools

Description

XY^- mice with the dl1Rlb allele in the sex determining region of the Y chromosome (Sry) gene, are phenotypic gonadal females. XX Tg(Sry)2Ei mice carrying the Tg(Sry)2Ei transgene are phenotypic gonadal males. The combination of these two mutations produces four "core" genotypes that may be useful in the study of the interaction of sex chromosomes and gonadal type that influences phenotypic characteristics.

Detailed description

The dl1Rlb allele (Y^-) is an 11 kb deletion in the sex determining region of the Y chromosome, Sry , XY^- mice (with ovaries) with this mutation are phenotypic gonadal females, although they lose germ cells and cease estrous cycling earlier in life. The donating investigator indicates that XY^- mice are generally infertile on the C57BL/6 background. XX mice carrying the Tg(Sry)2Ei transgene are phenotypic gonadal males (with testes), although they lack sperm and have smaller testes than normal males. When the two mutations are combined, testis determination is transferred from the Y chromosome to an autosome. Mating the carrier male to a C57BL/6J female produces four "core" genotypes that can be used as a model to investigate relationships between sex chromosome complement (XX or XY) and gonadal type that influences phenotypic characteristics. The four genotypes produced are two types of gonadal females (XX, XY^-), and two types of gonadal males (XXTg(Sry), XY^- Tg(Sry)).

Four core genotypes:
XX normal females (+/+)
XY Sry^dl1Rlb phenotypic females (+/Sry or XY^-)
XX Tg(Sry)2Ei phenotypic males (+/Tg(Sry2))
XY Sry^dl1Rlb Tg(Sry)2Ei phenotypic fertile males (Sry/Tg(Sry2))

Development

The Tg(Sry)2Ei transgenic construct was generated by Dr. Robin Lovell-Badge's laboratory from 129-derived 14.6-kb of genomic sequence encoding Sry. In the laboratory of Dr. Eva Eicher at the Jackson Laboratory, the construct was injected into the male pronuclei of fertilized eggs obtained from mating C57BL/6JEi females with C57BL/6JEi-Chr Y^AKR/J males. The XY transgenic male founder 2 was obtained and maintained by backcrossing transgenic males, obligatorily carrying the consomic Chr Y^AKR/J, to C57BL/6JEi females.

The dl1Rlb mutation arose spontaneously in a 129S6/SvEvTac derived-CCE embryonic stem cell line treated for retroviral integration. Chimeric male AL430 was mated to females from a C3H based random bred colony carrying the blotchy mutation. XY females produced by these matings were determined to be the result of a spontaneous 11 kb deletion in the Y chromosome and not a proviral insertion. These XY females were either sterile or extremely subfertile, and the continued maintenance of the stock was dependent on fertile XXY females generated by Dr. Paul Burgoyne. This mutation, originally termed Tdy^m1,, was first characterized in the laboratory of Dr. Robin Lovell-Badge, National Institute of Medical Research, London. The dl1Rlb mutation was transferred to an outbred MF1 background and then eventually combined with the Tg(Sry)2Ei transgene by Paul Burgoyne at NIMR, who mated XXY females (that generate X and XY eggs) to X (Paf labeled) Y transgenic males (that generate a low frequency of 'O' gametes with the Sry transgene) to produce the synthetically fertile XY dl1Rlb:Tg(Sry)2Ei males. When mated to normal XX females, the only fertile male offspring are those with the same genotype as the father. The mutation and transgene were backcrossed together into the C57BL/6J background for a minimum of eighteen generations. Dr. Arthur Arnold, UCLA, donated the strain to the Repository in 2009.

Allele

Symbol: Tg(Sry)2Ei
Name: transgene insertion 2, Eva M Eicher
MGI accession ID: MGI:3041982
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(Sry)2Ei
Marker name: transgene insertion 2, Eva M Eicher
Chromosome: 3
Strain of origin: C57BL/6JEi-Chr Y^AKR
Expressed genes: Sry,sex determining region of Chr Y,mouse, laboratory
Molecular note: This transgene consists of an inbred 129 strain derived 14.6 Kb genomic fragment containing the entire Sry open reading frame and no other genes.

Allele

Symbol: Sry^dl1Rlb
Name: sex determining region of Chr Y-deletion 1, Robin Lovell-Badge
MGI accession ID: MGI:1857786
Generation method: Spontaneous
Marker symbol: Sry
Marker name: sex determining region of Chr Y
Chromosome: Y
Strain of origin: 129S6/SvEvTac
Molecular note: This allele contains an 11 kb deletion in the testis-determining region of the gene, including a highly conserved exon encoding the HMG box domain.