B6.Cg-Tg(Sry)2Ei Sry^dl1Rlb T(XTmsb4x-Hccs;Y)1Dto/ArnoJ

Stock number: 010905
Product name: Four Core Genotypes (FCG)
Strain synonyms: Tdy ml, Four Core Genotypes, FCG
Research areas: Developmental Biology Research, Reproductive Biology Research, Research Tools

Description

Removal of this mouse colony is imminent. If live mice are needed for your studies, it is advised that they be ordered immediately. After removal, the mice will be available from a cryorecovery.

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.

For Stock No. 010905, the Y^Sry- chromosome also harbors a spontaneous translocation [T(XTmsb4x-Hccs;Y)1Dto] of a 3.2 MB region mapping to Chromosome X which contains nine annotated genes (Tmsb4x, Tlr8, Tlr7, Prps2, Frmpd4, Msl3, Arhgap6, Amelx and Hccs).

We are experiencing technical difficulties with our genotype descriptions for this strain. Please reference the table below to assist in selecting the genotype you wish to order:

GENOTYPE to select on pricing panel	Genotype Description [four core genotype list i-iv]
Sex "Male" Top (HEMI HEMI)	[iv] XY Srydl1Rlb Tg(Sry)2Ei [aka, XY-(Sry+), XY-Sry, XYM or XYT]: transgenic XY male with testis (gonadal male; normal male fertility). JAX genotyping scores "Srydl1Rlb/Tg(Sry)2Ei" meaning positive for Tg(Sry)2Ei and positive for Y chromosome.
Sex "Male" Bottom (HEMI NonCarrier)	[iii] XX Tg(Sry)2Ei [aka, XX(Sry+), XXSry, XXM or XXT]: transgenic XX with testis (gonadal male; infertile). JAX genotyping scores "+/Tg(Sry)2Ei" meaning positive for Tg(Sry)2Ei and negative for Y chromosome.
Sex "Female" Top (NonCarrier HEMI)	[ii] XY Srydl1Rlb [aka, XY-, XYF or XYO]: non-transgenic XY with ovaries (gonadal female; infertile). JAX genotyping scores "+/Srydl1Rlb" meaning negative for Tg(Sry)2Ei and positive for Y chromosome.
Sex "Female" Top (NonCarrier NonCarrier)	[i] XX wildtype [aka, XX, XXF or XXO]: non-transgenic XX female with ovaries (gonadal female; normal female fertility). JAX genotyping scores "+/+" meaning negative for Tg(Sry)2Ei and negative for Y chromosome.

Of note, a new strain, Stock No. 039108, was recovered from cryopreservation at the National Institute for Medical Research (NIMR) by Dr. James Turner (Crick Institute) prior to the spontaneous mutation and does not carry the translocation.

Detailed description

The dl1Rlb allele (Y^- or Y^Sry-) 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 (XX Tg(Sry)2Ei, XY^- Tg(Sry)2Ei).

This strain is maintained by breeding C57BL/6J females with XY Sry^dl1Rlb Tg(Sry)2Ei males. The resulting offspring can have one of the four core genotypes listed below:

[i] XX wildtype [aka, XX, XXF or XXO]: non-transgenic XX female with ovaries (gonadal female; normal female fertility). JAX genotyping scores "+/+" meaning negative for Tg(Sry)2Ei and negative for Y chromosome.

[ii] XY Sry^dl1Rlb [aka, XY^-, XYF or XYO]: non-transgenic XY with ovaries (gonadal female; infertile). JAX genotyping scores "+/Sry^dl1Rlb" meaning negative for Tg(Sry)2Ei and positive for Y chromosome.

[iii] XX Tg(Sry)2Ei [aka, XX(Sry+), XXSry, XXM or XXT]: transgenic XX with testis (gonadal male; infertile). JAX genotyping scores "+/Tg(Sry)2Ei" meaning positive for Tg(Sry)2Ei and negative for Y chromosome.

[iv] XY Sry^dl1Rlb Tg(Sry)2Ei [aka, XY^-(Sry+), XY^-Sry, XYM or XYT]: transgenic XY male with testis (gonadal male; normal male fertility). JAX genotyping scores "Sry^dl1Rlb/Tg(Sry)2Ei" meaning positive for Tg(Sry)2Ei and positive for Y chromosome.

In 2023, Dr. Duncan Odom (German Cancer Research Center - Panten J, et. al. BioRxiv 2023) determined that a 3.2 MB region mapping to ChrX:165.530.000-168.750.000 (GRCm39), which contains nine annotated genes (Tmsb4x, Tlr8, Tlr7, Prps2, Frmpd4, Msl3, Arhgap6, Amelx and Hccs), of which six are detectably upregulated in an FCG XY-biased manner, fused to the Y^Sry- chromosome. This spontaneous translocation [T(XTmsb4x-Hccs;Y)1Dto] likely occurred during the backcross of the strain to C57BL/6J in the lab of Arthur P. Arnold, who donated Stock No. 010905 to Jackson Laboratory in 2009.
In 2024, The Jackson Laboratory screened multiple cohorts of Stock No. 010905 for Tlr7 copy number (qPCR) and found all of the four core genotypes (listed above) had 2 copies of Trl7 - indicating the mutant Y chromosome (Y^-) does indeed harbor the translocation T(XTmsb4x-Hccs;Y)1Dto in addition to the Sry^dl1Rlb.

Of note, a new strain, Stock No. 039108, was recovered from cryopreservation at the National Institute for Medical Research (NIMR) by Dr. James Turner (Crick Institute) prior to the spontaneous mutation and does not carry the translocation.

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. In 2015, it was determined that 12-14 copies of the transgene inserted into chromosome 3 (Itoh Y, et al BMC Research Notes (2015) 8:69). The insertion deleted 74 bp of chromosome 3, but did not disrupt any known coding genes or pseudogenes.

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.

In 2023, Dr. Duncan Odom (German Cancer Research Center - Panten J, et. al. BioRxiv 2023) determined that a 3.2 MB region mapping to ChrX:165.530.000-168.750.000 (GRCm39), which contains nine annotated genes (Tmsb4x, Tlr8, Tlr7, Prps2, Frmpd4, Msl3, Arhgap6, Amelx and Hccs), of which six are detectably upregulated in an FCG XY-biased manner, fused to the Y^Sry- chromosome. This spontaneous translocation [T(XTmsb4x-Hccs;Y)1Dto] likely occurred during the backcross of the strain to C57BL/6J in the lab of Arthur P. Arnold, who donated Stock No. 010905 to Jackson Laboratory in 2009.
In 2024, The Jackson Laboratory screened multiple cohorts of Stock No. 010905 for Tlr7 copy number (qPCR) and found all of the four core genotypes (listed above) had 2 copies of Trl7 - indicating the mutant Y chromosome (Y^-) does indeed harbor the translocation T(XTmsb4x-Hccs;Y)1Dto in addition to the Sry^dl1Rlb.

Allele

Symbol: Tg(Sry)2Ei
Name: transgene insertion 2, Eva M Eicher
MGI accession ID: MGI:3041982
Generation method: Transgenic
Attributes: Inserted expressed sequence
Synonyms: Tg(Sry-129)2Ei
Marker symbol: Tg(Sry)2Ei
Marker name: transgene insertion 2, Eva M Eicher
Marker synonyms: Tg(Sry-129)2Ei
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
Synonyms: Sry^dl1Rob; Sry^m1; Tdy^m1; Y-; Y^Tdym1; Yq-del
Marker symbol: Sry
Marker name: sex determining region of Chr Y
Marker synonyms: SRXX1; SRXY1; Sry3; Sry3B; SRYGENE; TDF; TDY
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.

Allele

Symbol: T(XTmsb4x-Hccs;Y)1Dto
Name: translocation, Chr X, Duncan T Odom
MGI accession ID: MGI:7571197
Generation method: Spontaneous
Attributes: Not Applicable
Marker symbol: T(XTmsb4x-Hccs;Y)1Dto
Marker name: translocation, Chr X, Duncan T Odom
Chromosome: Y
Strain of origin: B6.Cg-Tg(Sry)2Ei Sry^dl1Rlb T(XTmsb4x-Hccs;Y)1Dto/ArnoJ
Molecular note: The translocation has a 3.2 MB region mapping to chrX:165.530.000 - 168.750.000 on GRCm39, and containing nine annotated genes (Tmsb4x, Tlr8, Tlr7, Prps2, Frmpd4, Msl3, Arhgap6, Amelx and Hccs), of which six are detectably upregulated, is fused to the Y chromosome.