C3Sn.AK-Del(17)T^hp Chr Y^AKR/J/EiJ

Stock number: 001053
Product name: hairpin tail

Description

This multigenic deletion, which includes T, Qk, and Igf2r, is valuable for studies of sex-reversal and maternal imprinting.

Detailed description

Del(17)T^hp is a 4 cM deletion that includes T, Qk, and Igf2r (Tme). The proximal breakpoint lies between D17Leh66E and D17Leh66EII and the distal breakpoint lies between D17Leh66D and D17Mit12. As with other T mutants, hemizygotes have a shortened tail and other axial skeleton defects, such as vertebral fusions and scoliosis, and homozygotes are embryonic lethal, but these homozygotes were reported by Bennett (1975) to die by E7, 3 days earlier than T/T homozygotes. Because the T-associated maternal effect (Tme) is part of this deletion, transmission of Del(17)T^hp from the male produces pups with normal viability and a variably short or kinked tail while transmission from the female parent results in viable wildtype pups but embryonic lethallty of carrier pups, with the few that are stillborn being oedematous with short, kinky tails and postaxial polydactyly. This lethality traces to the maternally-derived pups themselves, not the maternal environment since no viable carrier pups are obtained from hemizygous females bred to wildtype males, a reasonable percentage of carrier pups are born from wildtype females bred to hemizygous males, with some embryonic loss occurring, and intercrosses of hemizygous males with hemizygous females yield some viable hemizygous pups and some oedematous stillborn pups with postaxial polydatyly and short, kinky tails. Tme was defined by Wutz et al. (2001) as Igf2r, a maternally expressed imprinted gene encoding a receptor for both insulin-like growth factor and mannose 6-phosphate.

When on a C57BL/6J Chr Y^AKR/J background Del(17)T^hp hemizygotes have a high rate of sex-reversal, with XY^AKR/J Del(17)T^hp hemizygotes developing ovarian tissue or both ovarian and testicular tissue, but on the C3H/HeSnJ background testicular tissue develops even in the presence of the Chr Y^AKR/J with its variant Sry gene (Washburn et al., 1990; Bogani et al., 2009).

Development

The Del(17)T^hp multigenic deletion, formerly called T^hp, arose spontaneously in AKR/J at The Jackson Laboratory. Because maternally imprinted Igf2r is in this deletion, this deletion cannot be transmitted from carrier females. Instead, the laboratory of Dr. Eva Eicher backcrossed this deletion onto the C3H/HeSnJ background by breeding from a carrier male bred to a C3H/HeSnJ female at each generation and thereby capturing the Chr Yin this consomic. Even with the Chr Y^AKR/J this genetic background is not prone to sex reversal, but on a C57BL/6J background hemizygous Del(17)T^hp carriers that are XY^AKR/J have a high rate of failed testicular development, with half developing only ovarian tissue and half developing both ovarian and testicular tissue. Embryos were generated for cryopreservation from C3H/HeSnJ females bred to C3Sn.AK-Del(17)T^hp Chr Y^AKR/J males at generation N20.

Allele

Symbol: Del(17)T^hp
Name: deletion, Chr 17, T, hairpin tail
MGI accession ID: MGI:1856187
Generation method: Spontaneous
Synonyms: hairpin tail; Hp; T^hp
Marker symbol: Del(17)T^hp
Marker name: deletion, Chr 17, T, hairpin tail
Marker synonyms: T^hp
Chromosome: 17
Strain of origin: AKR/J
Molecular note: Restriction length polymorphisms and simple sequence variants were used to define the breakpoints of the deletion that comprises this allele. The proximal breakpoint of the deletion maps between D17Leh66EI and D17Leh66EII and the distal breakpoint is proximal to D17Mit122 but distal to D17Leh66D. The Qk locus is included in the deletion.
General note: Because this allele arose in the AKR/J inbred strain and can only be transmitted to viable offspring via a male carrier, all Del(17)T^hp strains carry the AKR Y Chromosome.