BTBR-Prkra^lear-5J Itpr3^tf/GrsrJ

Stock number: 027181
Research areas: Dermatology Research, Developmental Biology Research, Neurobiology Research

Description

This Prkra mutant has a dystonia phenotype not found in other Prkra mutants and provides a model for Dystonia 16.

Detailed description

On this BTBR background, mice homozygous for the little ear 5 Jackson mutation are distinctly smaller than their wildtype littermates, have ear pinnae that are less than half the normal size on average, have malformed skulls that are shorter than normal, and display ascending dystonia beginning at two weeks of age and progressing to death usually by three weeks of age, but no later than 6 weeks of age. The tail is finely kinked, but the bone structure appears normal and the tail tends to straighten out after death indicating the neurologic cause of the kinked tail. Many homozygotes display gnarled wrists and have impaired grasping reflex. An elongated step/push gait with the hind limbs was found in some homozygotes at three weeks of age. Some neurons in the dorsal root ganglia or trigeminal ganglion were found to be apoptotic or necrotic. The skull is shorter than normal, misshapen, and has incomplete ossification with many skulls having open foramen. Many of these phenotypes are dependent on genetic background.

Development

The little ear 5 Jackson mutation arose spontaneously in the BTBR T⁺ Itpr3^tf/J strain, which is homozygous for the tufted mutation. This mutant subline was maintained on this background homozygous for tufted, and Disc1^del and segregating for little ear 5 Jackson. Sperm was cryopreserved from males homozygous for tufted and heterozygous for little ear 5 Jackson and standard recovery is scheduled to use oocytes from BTBR T⁺ Itpr3^tf/J, which will generate pups homozygous for tufted and either wildtype or heterozygous for little ear 5 Jackson.

Allele

Symbol: Prkra^lear-5J
Name: little ears 5 Jackson
MGI accession ID: MGI:5692073
Generation method: Spontaneous
Marker symbol: Prkra
Marker name: protein kinase, interferon inducible double stranded RNA dependent activator
Chromosome: 2
Strain of origin: BTBR T⁺ Itpr3^tf/J
Molecular note: This spontaneous T insertion/duplication (an extra T in the poly(T) stretch) between chromosome 2 76,636,870-76 bp (GRCm38) causes a frameshift that introduces 7 novel amino acids followed by a premature stop codon.

Allele

Symbol: Itpr3^tf
Name: tufted
MGI accession ID: MGI:1857070
Generation method: Spontaneous
Marker symbol: Itpr3
Marker name: inositol 1,4,5-triphosphate receptor 3
Chromosome: 17
Strain of origin: BTBR
Molecular note: Complementation mapping was used to demonstrate that this spontaneous mutation was an allele of Itpr3. Sequencing revealed a 12 bp deletion in Exon23 (Chr17: 27238069, Build 38.1) which codes for amino acids 983-986. This mutation arose early in the history of the BTBR strain (in or soon after 1956) and is not found in 18 other strains (129P2/OlaHsd, 129S1/SvImJ, 129S5/SvEvBrd, A/J, AKR/J, BALB/cJ, C3H/HeJ, C57BL/6NJ, CAST/EiJ, CBA/J, DBA/2J, FVB/NJ, LP/J, NOD/ShiLtJ, NZO/HlLtJ, PWK/PhJ, SPRET/EiJ and WSB/EiJ)
General note: This allele was recovered from a Harwell testing stock carrying multiple recessive markers in an undefined background. (J:273)

Allele

Symbol: Disc1^del
Name: deletion
MGI accession ID: MGI:3623217
Generation method: Spontaneous
Marker symbol: Disc1
Marker name: disrupted in schizophrenia 1
Chromosome: 8
Strain of origin: various
Molecular note: A 25 bp deletion in exon 6 causes a frame shift in the reading frame, resulting in 13 novel amino acids and a premature stop codon in exon 7.
General note: This deletion appears in multiple strains of the 129 superfamily, 101/RI, BTBR T⁺ tf/J, LP/J, FVB/NJ, SJL/J, SWR/J and DDY/JclSidSeyFrkJ (J:111837, J:195189).