B6EiC3-+ a/Lnpk^Ul A/J

Stock number: 000557
Product name: ulnaless
Research areas: Developmental Biology Research

Description

These mice carry a radiation induced mutation at the Lnpk locus characterized by severe abnormalities in all four limbs.

Detailed description

The ulnaless mutation (Ul) causes severe abnormalities in all four limbs, but no abnormalities in the axial or cranial skeleton in either heterozygotes or homozygotes. Heterozygotes have an extreme reduction in the size of the radius and ulna with deformed fibulas, which are shortened and detached from the tibia, and tibias, which are generally bowed, and tibia and fibula are generally rotated approximately 90 degrees. Male heterozygotes fail to mate on this predominantly B6;C3H genetic background, but they appear to have normal gametogenesis and Peichel et al successfully used sperm from heterozygous males in in vitro fertilization. Fewer than the 50% expected heterozygotes are observed in the offspring of heterozygote x wildtype crosses on this background and this is due to prenatal and neonatal death. Females are more likely to die perinatally than are males. Homozygotes, assessed on a genetic background that included MOLF/Ei and FVB/N, have a more severe phenotype than heterozygotes, affecting the same skeletal components. The radius is shorter, there is no ossification center of the ulna, and there is a more severe loss of the fibula.

Development

The ulnaless mutation was identified in the progeny of an HT linkage testing stock female (homozygous for a, Gdf5^bp Sqk3^fz Mlph^ln Bloc1s6^pa and Ap3b1^pe) bred with a (C3H/HeJ x 101/H)F1 male that had received two 500 rad doses of X-rays 24 hours apart. This mutation was then maintained by breeding a heterozygote to a (C3H/HeJ x 101/H)F1, and was imported from Harwell into The Jackson Laboratory by Dr. Eva Eicher after 1968 and prior to 1970. At some point in the 1970?s it was maintained by breeding female heterozygotes to (C57BL/6J x CsH/HeJ)F1 males, such that in 1986 it reached generation N20. In 1984 embryos were generated for cryopreservation by breeding female heterozygotes at generation N13 with C57BL/6JEi males.

Allele

Symbol: a
Name: nonagouti
MGI accession ID: MGI:1855937
Generation method: Spontaneous
Marker symbol: a
Marker name: nonagouti
Marker synonyms: agouti; agouti signal protein; AGSW; AGTI; AGTIL; As; ASP; SHEP9
Chromosome: 2
Strain of origin: old mutant of the mouse fancy
Molecular note: Characterization of this allele shows an insertion of DNA comprised of a 5.5kb virus-like element, VL30, into the first intron of the agouti gene. The VL30 element itself contains an additional 5.5 kb sequence, flanked by 526 bp of direct repeats (beta4 retroviral sequence). The host integration site is the same as for a^t-2Gso and A^w-38J and includes a duplication of four nucleotides of host DNA and a deletion of 2 bp from the end of each repeat. Northern analysis of mRNA from skin of homozygotes shows a smaller agouti message and levels 8 fold lower than found in wild-type.
General note: Insertion of the LV30 retrotransposon without the beta4 retrovirus sequence does not cause the nonagouti phenotype. J:278039

Allele

Symbol: A
Name: wild-type agouti
MGI accession ID: MGI:1856464
Generation method: Spontaneous
Synonyms: dark-bellied agouti
Marker symbol: a
Marker name: nonagouti
Marker synonyms: agouti; agouti signal protein; AGSW; AGTI; AGTIL; As; ASP; SHEP9
Chromosome: 2
Strain of origin: various
Molecular note: This allele, often referred to as wild-type, comprises a novel 131 amino acid protein encoded in a gene comprising four exons, three coding, spanning 18kb. Unique changes in this gene account for all other alleles that have been molecularly characterized. The expression of this allele is almost always dominant to other alleles of this gene.
General note: The A allele is usually regarded as a wild-type allele. For example,the C3H and CBA mouse sublines are homozygous for agouti. Hairs are black with a subapical yellow band. This black-yellow-black pattern is referred to as agouti. The general appearance is yellowish brown, slightly lighter on the belly than on the back.

Allele

Symbol: Lnpk^Ul
Name: ulnaless
MGI accession ID: MGI:1857660
Generation method: Radiation induced
Synonyms: Ul
Marker symbol: Lnpk
Marker name: lunapark, ER junction formation factor
Marker synonyms: 2310011O18Rik; 4921514L11Rik; 9530051D01Rik; KIAA1715; Lnp; LNP1; Lnpk1; lunapark; NEDEHCC; Ul; ulnaless
Chromosome: 2
Strain of origin: (C3H/HeJ x 101/H)F1
Molecular note: The ulnaless mouse has been characterized as a paracentric inversion with a centromeric breakpoint into the lunapark gene and a telomeric breakpoint 770 kb away. This inversion disrupts the lunapark gene and increases the distance between the neighboring HoxD cluster and a cluster of enhancer sequences controlling several distinct genes over a large region. Genes Evx2, Hoxd12 and Hoxd13 are all misexpressed in the limb buds and genital buds of the ulnaless mouse. The inverted DNA includes Evx2, the HoxD complex, Mtx2, as well as some pseudogenes.