Mice with gene targetted prion protein alterations show that Prnp, Sine and Prni are congruent

Moore, Richard C.; Hope, James; McBride, Patricia; McConnell, I.; Selfridge, Jim; Melton, David W.; Manson, Jean

doi:10.1038/ng0298-118

Cited by 173 publications

(110 citation statements)

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“…The results of Houston et al (2002) indicate differences in average incubation period among different genotypes for Cheviot and Dorset animals that were infected artificially by a subcutaneous inoculation with SSBP/1. In addition, Moore et al (1998) found an association between the genotype of PrP and incubation period in mice.…”

Section: Effect Of Prp Genotypementioning

confidence: 99%

“…It has also been demonstrated that there is an interaction between the genotype of the host and the scrapie strain (Goldmann et al, 1994;O'Rourke et al, 1997; Barron et al, 2003). In the mouse, the incubation period of the disease has been associated with the PrP genotype (Moore et al, 1998) and with the prion strain inoculated (Bruce et al, 1991). However, polymorphism of the Prnp gene does not explain the total variation in incubation period that is observed, indicating the existence of other environmental and genetic factors that are involved in the disease.…”

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confidence: 99%

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Polygenic variation and transmission factors involved in the resistance/susceptibility to scrapie in a Romanov flock

Díaz

Vitezica

Rupp

et al. 2005

Journal of General Virology

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Data from 4049 Romanov sheep belonging to a flock affected by natural scrapie were analysed by using survival-analysis techniques. Failure time was defined as the period of time between first exposure to infection and the date that animals left the flock with scrapie signs. Four hundred and forty-seven sheep were identified as 'scrapie animals'. Several models, including level of exposure as a time-dependent effect, PrP genotype, sex, age at first exposure, litter size and factors related to vertical transmission, were tested. The best model was extended to a sire-dam frailty model, in order to estimate the polygenic variation in addition to that in the Prnp gene. A combined effect of rearing type and the dam's disease status was detected. Thus, only sheep with a low degree of exposure to infection as lambs (lambs reared artificially and born out of a healthy dam) showed less risk than others. Animals first exposed to infection at older ages seemed to be less susceptible to scrapie. In this Romanov population, new genotypes (AHQ/AHQ, AHQ/VRQ, ARR/VRQ and ARR/ARQ) were associated with risk, suggesting the effect of genotypes on the incubation period of animals. Polygenic variance was responsible for 21 % of the total genetic variability that was related to susceptibility to scrapie. Therefore, the genetic susceptibility to scrapie may be explained by the joint effect of point mutations at the Prnp major gene and a number of genes that modulate its effect. INTRODUCTIONTransmissible spongiform encephalopathies (TSEs), or prion diseases, are a group of fatal degenerative disorders of the central nervous system. They comprise a group of diseases that affect many species. TSEs are characterized by the accumulation of an abnormal isoform of the cellular prion protein, named PrP Sc . Scrapie is a TSE affecting sheep and goats. TSE in sheep, as in mice and humans, is controlled genetically (Hunter et al., 1989;Hunter, 1997;Prusiner & Scott, 1997;Elsen et al., 1999). Susceptibility to scrapie, which may be evaluated by mortality rate and incubation period, is mainly controlled by polymorphisms in the Prnp gene. Several point mutations located at codons 136 (T, A, V), 154 (R, H) and 171 (R, Q, H, K) of the gene have been associated with natural scrapie (e.g. Hunter, 1997). The ARR allele is associated with resistance and VRQ is associated with susceptibility (e.g. Hunter et al., 1996;Elsen et al., 1999). However, there are alleles, such as ARQ, ARH and AHQ, that behave differently depending on the breed (e.g. Hunter, 1997;Thorgeirsdottir et al., 1999). It has also been demonstrated that there is an interaction between the genotype of the host and the scrapie strain (Goldmann et al., 1994;O'Rourke et al., 1997; Barron et al., 2003). In the mouse, the incubation period of the disease has been associated with the PrP genotype (Moore et al., 1998) and with the prion strain inoculated (Bruce et al., 1991). However, polymorphism of the Prnp gene does not explain the total variation in incubation period that is observed, indicati...

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Section: Effect Of Prp Genotypementioning

confidence: 99%

mentioning

confidence: 99%

Polygenic variation and transmission factors involved in the resistance/susceptibility to scrapie in a Romanov flock

Díaz

Vitezica

Rupp

et al. 2005

Journal of General Virology

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“…The PrP gene is identical to the scrapie incubation period (Sip) gene (Dickinson & Outram, 1988 ;Moore et al, 1998). In all breeds studied, an amino acid change from glutamine (Q) to arginine (R) at codon 171 in the PrP gene renders the animal more resistant towards natural and experimental scrapie as well as experimental bovine spongiform encephalopathy , and only a single case of scrapie has been reported in sheep with a homozygous RR "(" PrP genotype (Ikeda et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Prion protein gene polymorphisms in sheep with natural scrapie and healthy controls in Norway.

Tranulis¹,

Osland²,

Bratberg

et al. 1999

Journal of General Virology

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Two-hundred and forty healthy sheep and 32 cases of natural scrapie in Norway were analysed for disease-linked polymorphisms in the prion protein (PrP) gene. Scrapie was strongly associated with the presence of a valine polymorphism at codon 136 (V 136 ), as 68n8 % of the cases were homozygous (VV 136 ) and 15n6 % were valine/alanine heterozygous (VA 136 ). All cases were homozygous arginine/arginine at codon 154 (RR 154 ), except two which were homozygous histidine/histidine (HH 154 ). All cases except two were homozygous glutamine/glutamine at codon 171 (QQ 171 ), the two exceptions being heterozygous glutamine/arginine (QR 171 ). More than 80 % of all scrapie cases in Norway have occurred in a Cheviot-related crossbred type of sheep called Rygja. This type of sheep, which is largely restricted to the south-western coast, carries the V 136 allele at a higher frequency than do other breeds of Norwegian sheep. Polymorphisms at codons 138 and 151 are also described.

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“…The characteristic of TSE is the accumulation of PrP sc (pathological protease-resistant isoform), which is generated as a result of post-translational modification and changed in the stereochemical conformation of host-encoded, cellular prion proteins (PrP c ) (Prusiner 1998). According to reports, the polymorphisms of PRNP have been shown to influence incubation and the susceptibility of these diseases such as BSE and the incubation period in humans (Shibuya et al 1998;Shi et al 2016), mice (Moore et al 1998;Aguilar-Calvo et al 2014), goats (Vitale et al 2016), sheep (Stepanek and Horin 2017) and buffaloes (Yaman et al 2017).…”

Section: Introductionmentioning

confidence: 99%

The evaluation of 23-bp and 12-bp insertion/deletion within the PRNP gene and their effects on growth traits in healthy Chinese native cattle breeds

Yang

Zhang

Liu

et al. 2017

Journal of Applied Animal Research

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Polymorphisms in the prion protein gene (PRNP) have been linked with the occurrence of transmissible spongiform encephalopathies and the expression of some phenotypic traits in healthy animals including cattle. The aim of this study was to verify the 23-bp insertion/deletion (indel) within promoter region and the 12-bp indel within intron 1 of PRNP, as well as to evaluate their associations with growth traits. Two loci of PRNP were genotyped in 1558 healthy Chinese cattle sampled from 6 indigenous breeds. Moreover, phenotypic records for growth were used to find the relationship between PRNP polymorphisms and phenotypic performance. The results confirmed the occurrence of these two indel polymorphisms in the analysed breeds. Association analysis showed that the 23-bp indel was significantly related to the body length and heart girth in 18-months-old Nanyang cattle. The 12-bp indel was significantly related to the growth traits in three cattle breeds, such as the body weight in Xia'nan cattle, the daily gained weight in 12-months-old Nanyang cattle and the cannon circumference and rump length in Ji'an cattle. These findings indicated that these two indels may affect bovine growth traits, which could benefit to healthy cattle selection and breeding through marker-assisted selection.

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Mice with gene targetted prion protein alterations show that Prnp, Sine and Prni are congruent

Cited by 173 publications

References 48 publications

Polygenic variation and transmission factors involved in the resistance/susceptibility to scrapie in a Romanov flock

Polygenic variation and transmission factors involved in the resistance/susceptibility to scrapie in a Romanov flock

Prion protein gene polymorphisms in sheep with natural scrapie and healthy controls in Norway.

The evaluation of 23-bp and 12-bp insertion/deletion within the PRNP gene and their effects on growth traits in healthy Chinese native cattle breeds

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