GM2 Gangliosidosis in Shiba Inu Dogs with an In‐Frame Deletion in HEXB

Consistent with a tentative diagnosis of neuronal ceroid lipofuscinosis (NCL), autofluorescent cytoplasmic storage bodies were found in neurons from the brains of 2 related Shiba Inu dogs with a young‐adult onset, progressive neurodegenerative disease. Unexpectedly, no potentially causal NCL‐related variants were identified in a whole‐genome sequence generated with DNA from 1 of the affected dogs. Instead, the whole‐genome sequence contained a homozygous 3 base pair (bp) deletion in a coding region of HEXB. The other affected dog also was homozygous for this 3‐bp deletion. Mutations in the human HEXB ortholog cause Sandhoff disease, a type of GM2 gangliosidosis. Thin‐layer chromatography confirmed that GM2 ganglioside had accumulated in an affected Shiba Inu brain. Enzymatic analysis confirmed that the GM2 gangliosidosis resulted from a deficiency in the HEXB encoded protein and not from a deficiency in products from HEXA or GM2A, which are known alternative causes of GM2 gangliosidosis. We conclude that the homozygous 3‐bp deletion in HEXB is the likely cause of the Shiba Inu neurodegenerative disease and that whole‐genome sequencing can lead to the early identification of potentially disease‐causing DNA variants thereby refocusing subsequent diagnostic analyses toward confirming or refuting candidate variant causality.     

A Homozygous KCNJ10 Mutation in Jack Russell Terriers and Related Breeds with Spinocerebellar Ataxia with Myokymia,Seizures, or Both

Background

Juvenile‐onset spinocerebellar ataxia has been recognized in Jack Russell Terriers and related Russell group terriers (RGTs) for over 40 years. Ataxia occurs with varying combinations of myokymia, seizures, and other signs of neurologic disease. More than 1 form of the disease has been suspected.

Hypothesis/Objectives

The objective was to identify the mutation causing the spinocerebellar ataxia associated with myokymia, seizures, or both and distinguish the phenotype from other ataxias in the RGTs.

Animals

DNA samples from 16 RGTs with spinocerebellar ataxia beginning from 2 to 12 months of age, 640 control RGTs, and 383 dogs from 144 other breeds along with the medical records of affected dogs were studied.

Methods

This case‐control study compared the frequencies of a KCNJ10 allele in RGTs with spinocerebellar ataxia versus control RGTs. This allele was identified in a whole‐genome sequence of a single RGT with spinocerebellar ataxia and myokymia by comparison to whole‐genome sequences from 81 other canids that were normal or had other diseases.

Results

A missense mutation in the gene coding for the inwardly rectifying potassium channel Kir4.1 (KCNJ10:c.627C>G) was significantly (P < .001) associated with the disease. Dogs homozygous for the mutant allele all had spinocerebellar ataxia with varying combinations of myokymia and seizures.

Conclusions and Clinical Importance

Identification of the KCNJ10 mutation in dogs with spinocerebellar ataxia with myokymia, seizures, or both clarifies the multiple forms of ataxia seen in these breeds and provides a DNA test to identify carriers.     

Homozygous PPT1 Splice Donor Mutation in a Cane Corso Dog With Neuronal Ceroid Lipofuscinosis

A 10‐month‐old spayed female Cane Corso dog was evaluated after a 2‐month history of progressive blindness, ataxia, and lethargy. Neurologic examination abnormalities indicated a multifocal lesion with primarily cerebral and cerebellar signs. Clinical worsening resulted in humane euthanasia. On necropsy, there was marked astrogliosis throughout white matter tracts of the cerebrum, most prominently in the corpus callosum. In the cerebral cortex and midbrain, most neurons contained large amounts of autofluorescent storage material in the perinuclear area of the cells. Cerebellar storage material was present in the Purkinje cells, granular cell layer, and perinuclear regions of neurons in the deep nuclei. Neuronal ceroid lipofuscinosis (NCL) was diagnosed. Whole genome sequencing identified a PPT1c.124 + 1G>A splice donor mutation. This nonreference assembly allele was homozygous in the affected dog, has not previously been reported in dbSNP, and was absent from the whole genome sequences of 45 control dogs and 31 unaffected Cane Corsos. Our findings indicate a novel mutation causing the CLN1 form of NCL in a previously unreported dog breed. A canine model for CLN1 disease could provide an opportunity for therapeutic advancement, benefiting both humans and dogs with this disorder.     

The influence of trees on soil fertility on two contrasting semi-arid soil types at Matopos,Zimbabwe

An investigation into the influence of indigenous trees on soil fertility was conducted in an area of semi-arid tropical savanna in Zimbabwe on two contrasting soil types: dystrophic savanna soils (sandy soils) and eutrophic savanna soils (fine-textured soils). The study adds further support to the growing literature showing that trees have a positive influence on soil fertility. The study suggests that tree clearance, as advocated in these agropastoral systems, may not necessarily result in long-term benefits. It is argued that the primary mechanism by which soil fertility is improved is through increased litter and soil organic matter compartments under trees. The influence of trees on cation levels is greater on sandy soils than fine-textured soils because the exchange capacity of fine-textured soils is determined largely by soil texture whereas organic matter is the prime determinant of exchange capacity in sandy soils. The present study demonstrates that fertility improvement under trees is not at the expense of fertility decline in the surface soils of the zone around the tree. Leaf quality, as reflected simply in leaf C:N ratio, influences decomposition rates but the activities of termites probably confound any simple relationship. Litter quality of tree species is probably important in determining levels of soil organic matter under canopies, with higher levels under species with lower leaf quality.     

The nutritive value of marula (Sclerocarya birrea) seed cake for broiler chickens: nutritional composition,performance, carcass characteristics and oxidative and mycotoxin status

This study was aimed at investigating the nutritive value of marula seed cake (MSC) as an alternative protein source for broilers. In a completely randomised design involving six replicate pens of five chickens assigned to each of five treatments, body weight gain (BWG), feed intake (FI), feed conversion efficiency (FCE) and carcass characteristics were measured in an experiment in which 150 28-day-old broilers were fed maize-based diets containing, respectively, 0, 5, 10, 15 and 20% MSC at finisher phase. The results showed MSC to be remarkably high in CP (470.0 g/kg DM) and EE (343.5 g/kg DM), with moderate CF (58.2 g/kg DM), ash (54.3 g/kg DM), Ca (1.1 g/kg DM) and P (11.0 g/kg DM). Whilst very poor in lysine, MSC was found to be rich in methionine, cyst(e)ine, arginine and glutamic acid; it also contains good levels of valine, glycine, threonine, isoleucine, leucine, histidine, phenylalanine, serine, proline and alanine. Also, it contained 85.24% oleic (OA), 9.65% palmitic and 5.11% stearic acids, with a high peroxide value and low levels of mycotoxins deoxynivalenol (DON) and T-2 toxin. BWG, FI and FCE of broiler chickens significantly decreased (P < 0.001) as the dietary level of MSC increased. Further, dietary MSC significantly decreased bird live weight at slaughter (P < 0.001), plucked weight (P < 0.001), dressed weight (P < 0.001) and weights of the liver (P < 0.001) and neck (P < 0.05). The results therefore demonstrate MSC to be a good source of CP, fat, Ca, P, amino acids (except lysine) and OA that can replace soya bean meal (SBM) in broiler diets. However, its use is currently limited by lipid peroxidation and presence of mycotoxins.