Prime Editor-mediated Correction of a Pathogenic Mutation in Purebred Dogs

Abstract Canine hip dysplasia (HD) is a multifactorial disease caused by interactions between genetic and environmental factors. HD, which mainly occurs in medium- to large-sized dogs, is a disease that causes severe pain and requires surgical intervention. However, the procedure is not straight-forward, and the only way to ameliorate the situation is to exclude individual dogs with HD from breeding programs. Recently, prime editing (PE), a novel genome editing tool based on the CRISPR-Cas9 system, has been developed and validated in plants and mice. In this study, we successfully corrected a mutation related to HD in Labrador retriever dogs for the first time. We collected cells from a dog diagnosed with HD, corrected the mutation using PE, and generated mutation-corrected dogs by somatic cell nuclear transfer. The results indicate that PE technology can potentially be used as a platform to correct genetic defects in dogs.

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Acetabular deepening in the treatment of severe canine hip dysplasia

Pesquisa Veterinária Brasileira ◽

10.1590/s0100-736x2009000200014 ◽

2009 ◽

Vol 29 (2) ◽

pp. 163-166

Author(s):

Paulo Iamaguti ◽

Luciana S. Iamaguti ◽

Raquel Sartor

Keyword(s):

Femoral Head ◽

Hip Dysplasia ◽

Surgical Intervention ◽

Good Alternative ◽

Joint Capsule ◽

Two Phases ◽

Canine Hip Dysplasia

A technique to restore acetabular anatomy by deepening the acetabular cavity and reconstructing the femoral head ligament and the joint capsule was tested on nine large breed dogs with severe hip dysplasia and acute subdislocation or dislocation. The technique consisted of two phases. First, all dogs were submitted to bilateral pectinotomy. In a second surgical intervention on the same dogs the acetabulum was approached and deepened, and the femoral head ligament and the joint capsule were reconstructed. In general, within 30 days of the surgery dogs could stand on the operated member to walk. Except for two dogs, all the others recovered pelvic member locomotive ability within 60-90 days after surgery. It is concluded that acetabuloplasty is a good alternative for treatment of severe canine hip dysplasia.

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Evaluation of Sacroiliac Wedge Rotation to Increase Acetabular Ventroversion

Veterinary and Comparative Orthopaedics and Traumatology ◽

10.1055/s-0038-1632486 ◽

1999 ◽

Vol 12 (04) ◽

pp. 173-177 ◽

Cited By ~ 2

Author(s):

R. L. Aper ◽

M. D. Brown ◽

M. G. Conzemius

Keyword(s):

Hip Joint ◽

Hip Dysplasia ◽

Clinical Effect ◽

Pelvic Osteotomy ◽

Alternative Method ◽

Angular Measurements ◽

Si Joint ◽

In Vivo Effects ◽

Canine Hip Dysplasia

SummaryTreatment of canine hip dysplasia (CHD) via triple pelvic osteotomy (TPO) is widely accepted as the treatment that best preserves the existing hip joint. TPO, however, has several important disadvantages. In an effort to avoid some of the difficulties associated with TPO an alternative method of creating acetabular ventroversion (AW) was sought. The purpose of this study was to explore the effects of placement of a wedge in the sacroiliac (SI) joint on A W and to compare this to the effect of TPO on A W . On one hemipelvis a 30° pelvic osteotomy plate was used for TPO. The contralateral hemipelvis had a 28° SI wedge inserted into the SI joint. Pre- and postsurgical radiographs of each pelvis were taken and the angular measurements were recorded. On average, the 28° SI wedge resulted in 20.9° of A W, the 30° canine pelvic osteotomy plate resulted in 24.9° A W . Significant differences were not found (p >0.05) between the two techniques. Sacroiliac wedge rotation effectively creates A W and has several theoretical advantages when compared to TPO. The in vivo effects of sacroiliac wedge rotation should be studied in order to evaluate the clinical effect of the technique.Sacroiliac wedge rotation was tested as an alternative method to increase the angle of acetabular ventroversion. This technique effectively rotated the acetabulum and has several theoretical advantages when compared to triple pelvic osteotomy.

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Canine Hip Dysplasia in Sweden

Acta Radiologica ◽

10.3109/05678067209174013 ◽

1972 ◽

Vol 12 ◽

pp. 175-180 ◽

Cited By ~ 1

Author(s):

Bengt Henricson ◽

Gunnela Ljunggren ◽

Sten-Erik Olsson

Keyword(s):

Hip Dysplasia ◽

Canine Hip Dysplasia

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Efficient TALEN-mediated gene knockin at the bovine Y chromosome and generation of a sex-reversal bovine

Cellular and Molecular Life Sciences ◽

10.1007/s00018-021-03855-1 ◽

2021 ◽

Author(s):

Ming Wang ◽

ZhaoLin Sun ◽

Fangrong Ding ◽

Haiping Wang ◽

Ling Li ◽

...

Keyword(s):

Y Chromosome ◽

Nuclear Transfer ◽

Sex Reversal ◽

Practical Application ◽

Transcription Activator ◽

New Methods ◽

Fetal Fibroblasts ◽

Male Phenotype ◽

Solid Foundation ◽

First Time

AbstractFunctional elucidation of bovine Y-chromosome genes requires available genome editing technologies. Meanwhile, it has yet to be proven whether the bovine Sry gene is the main or single factor involved in the development of the male phenotype in bovine. Here, we efficiently knocked out four Y-linked genes (Sry, ZFY, DDX3Y, and EIF2S3Y) in bovine fetal fibroblasts (BFFs) with transcription activator-like effector nucleases (TALENs) individually. Furthermore, we used TALEN-mediated gene knockin at the Sry gene and generated a sex-reversal bovine by somatic cell nuclear transfer (SCNT). The resulting bovine had only one ovary and was sterile. We demonstrate, for the first time, that the Sry gene is an important sex-determining gene in bovine. Our method lays a solid foundation for detecting the biology of the bovine Y chromosome, as it may provide an alternative biological model system for the study of mammalian sex determination, and new methods for the practical application in agricultural, especially for sex predetermination.

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Integrating metabolomics and targeted gene expression to uncover potential biomarkers of fungal/oomycetes-associated disease susceptibility in grapevine

Scientific Reports ◽

10.1038/s41598-020-72781-2 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 1

Author(s):

Marisa Maia ◽

António E. N. Ferreira ◽

Rui Nascimento ◽

Filipa Monteiro ◽

Francisco Traquete ◽

...

Keyword(s):

Gene Expression ◽

Plant Defence ◽

Breeding Programs ◽

Analysis Group ◽

Expression Of Genes ◽

Leucoanthocyanidin Reductase ◽

Defence Responses ◽

Targeted Gene Expression ◽

Plant Defence Responses ◽

First Time

Abstract Vitis vinifera, one of the most cultivated fruit crops, is susceptible to several diseases particularly caused by fungus and oomycete pathogens. In contrast, other Vitis species (American, Asian) display different degrees of tolerance/resistance to these pathogens, being widely used in breeding programs to introgress resistance traits in elite V. vinifera cultivars. Secondary metabolites are important players in plant defence responses. Therefore, the characterization of the metabolic profiles associated with disease resistance and susceptibility traits in grapevine is a promising approach to identify trait-related biomarkers. In this work, the leaf metabolic composition of eleven Vitis genotypes was analysed using an untargeted metabolomics approach. A total of 190 putative metabolites were found to discriminate resistant/partial resistant from susceptible genotypes. The biological relevance of discriminative compounds was assessed by pathway analysis. Several compounds were selected as promising biomarkers and the expression of genes coding for enzymes associated with their metabolic pathways was analysed. Reference genes for these grapevine genotypes were established for normalisation of candidate gene expression. The leucoanthocyanidin reductase 2 gene (LAR2) presented a significant increase of expression in susceptible genotypes, in accordance with catechin accumulation in this analysis group. Up to our knowledge this is the first time that metabolic constitutive biomarkers are proposed, opening new insights into plant selection on breeding programs.

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The PennHIP method of predicting canine hip dysplasia

In Practice ◽

10.1136/inp.f7486 ◽

2014 ◽

Vol 36 (2) ◽

pp. 66-74 ◽

Cited By ~ 1

Author(s):

Mike Guilliard

Keyword(s):

Hip Dysplasia ◽

Canine Hip Dysplasia

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Unlocking the genetic make-up of canine hip dysplasia: We can work it out

The Veterinary Journal ◽

10.1016/j.tvjl.2009.02.007 ◽

2009 ◽

Vol 181 (2) ◽

pp. 77-78 ◽

Cited By ~ 3

Author(s):

Hannes Lohi ◽

Frank W. Nicholas

Keyword(s):

Hip Dysplasia ◽

Canine Hip Dysplasia

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Volume of the ligamentum capitis femoris in osteoarthritic hip joints of adult dogs

Journal of the South African Veterinary Association ◽

10.4102/jsava.v74i1.489 ◽

2003 ◽

Vol 74 (1) ◽

Cited By ~ 2

Author(s):

J.D. Mande ◽

P.M.F. Mbithi ◽

S.W. Mbugua ◽

I.B.J. Buoro ◽

P.K. Gathumbi

Keyword(s):

General Anaesthesia ◽

Crucial Role ◽

Hip Dysplasia ◽

Inverse Correlation ◽

Water Displacement ◽

Hip Joints ◽

Ligamentum Capitis Femoris ◽

The Mean ◽

Canine Hip Dysplasia

Ventrodorsal pelvic radiographs were made of 32 adult dogs under general anaesthesia. The hip joints were evaluated according to the severity of osteoarthritic changes graded as 0, 1, 2 or 3. The dogs were euthanased, the hip joints opened and the ligamentum capitis femoris dissected out in toto. The volume of each ligament was determined using a water displacement technique and the mean volume compared to the four radiographic grades of osteoarthritis. There was an inverse correlation (r = -0.75) between the mean volume of the ligamentum capitis femoris and the increasing severity of osteoarthritis as assessed by radiography. The results confirmed the crucial role of radiography in the clinical evaluation of hip dysplasia and osteoarthritis in the adult dog. Assessment of the volume of the ligamentum capitis femoris revealed that it is an important tool for research in canine hip dysplasia and osteoarthritis.

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