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.
Arthur P Arnold, UCLA
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 Srydl1Rlb phenotypic females (+/Sry or XY-)
XX Tg(Sry)2Ei phenotypic males (+/Tg(Sry2)
XY Srydl1Rlb Tg(Sry)2Ei phenotypic fertile males (Sry/Tg(Sry2)
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 YAKR/J males. The XY transgenic male founder 2 was obtained and maintained by backcrossing transgenic males, obligatorily carrying the consomic Chr YAKR/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 Tdym1,, 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.
|Expressed Gene||Sry, sex determining region of Chr Y, mouse, laboratory|
|Site of Expression|
|Site of Expression|
|Allele Name||transgene insertion 2, Eva M Eicher|
|Allele Type||Transgenic (Inserted expressed sequence)|
|Gene Symbol and Name||Tg(Sry)2Ei, transgene insertion 2, Eva M Eicher|
|Promoter||Sry, sex determining region of Chr Y, mouse, laboratory|
|Expressed Gene||Sry, sex determining region of Chr Y, mouse, laboratory|
|Strain of Origin||C57BL/6JEi-Chr YAKR|
|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.|
|Mutations Made By|| |
Eva Eicher, The Jackson Laboratory
|Allele Name||sex determining region of Chr Y-deletion 1, Robin Lovell-Badge|
|Allele Synonym(s)||Srydl1Rob; Srym1; Tdym1; Y-; YTdym1; Yq-del|
|Gene Symbol and Name||Sry, sex determining region of Chr 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.|
While maintaining a live colony, these mice are bred as carrier male crossed to C57BL/6 female.
When using the B6.Cg-Tg(Sry)2Ei Srydl1Rlb/ArnoJ mouse strain in a publication, please cite the originating article(s) and include JAX stock #010905 in your Materials and Methods section.
|One pair minimum...XX are females that function normally, +/+XY with Sry<dl1Rlb> (which is a deletion of Sry on the Y Chr) are phenotypic females, +/Sry. Although these mice breed as females the litter size is very small and the number of oocytes greatly reduced, shortening reproductive lifespan. XX with Tg(Sry)2Ei are phenotypic males,Ò+/Tg(Sry)2Ó and are sterile sex reversed femalesXY with Sry<dl1Rlb> Tg(Sry)2Ei are phenotypic males, Sry/Tg(Sry)2 and are fertile.|
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