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Details of Models
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000001 Micropthalmia
Contact:
Dr. John McEwan
Agresearch Invermay
Private Bag 50034
Mosgiel 9053
Dunedin
NEW ZEALAND
Tel: +64 +03 489 3809
john.mcewan@agresearch.co.nz
Species / Breed: Ovine (Texel)
Inheritance Pattern: Autosomal recessive
Macroscopic Phenotype: Blindness. Optic globes are half normal size and optic nerve at chiasma is half normal diameter.
Enzyme Analysis: –
Molecular Analysis: Currently building a genetic map with markers every 20 cM.
Histology: Dysplastic lens, ciliary body, iris and retina.
Pathology: Poor myelation of optic nerve axons.
Comparative Features: Resembles lens aplasia in mice.
References:
Jolly, R.D. et al., Genetic disorders of sheep in New Zealand: A review and perspective. NZ Vet. J., 2004. 52(2): 52–64.
van der Linde-Sipman, J.S. et al., Morphology and morphogenesis of hereditary microphthalmia in Texel sheep. J Comp. Pathol., 2003. 128(4): 269–75.
Roe, W.D. et al., Micropthalmia in Texel lambs. NZ Vet. J., 2003. 51(4): 194–5.
000002 Cataracts
Contact:
Dr. John McEwan
Agresearch Invermay
Private Bag 50034
Mosgiel 9053
Dunedin
NEW ZEALAND
Tel: +64 +03 489 3809
john.mcewan@agresearch.co.nz
Species / Breed: Ovine
Inheritance Pattern: Autosomal dominant
Macroscopic Phenotype: Cloudiness of lens. Blindness.
Enzyme Analysis: Increased levels of calcium dependent protease (calpain).
Histology: Accumulation of insoluble protein.
Pathology: increased calpain levels cause breakdown of lens protein.
Comparative: Similar developmental process in humans.
References:
Jolly R.D. et al., Genetic disorders of sheep in New Zealand: A review and perspective. NZ Vet. J., 2004. 52(2): 52–64.
Brooks H.V. et al., An inherited cataract in New Zealand Romney sheep. NZ Vet. J., 1982. 30(8): 113–4.
000003 Carwell Muscling (Muscular Hypertrophy)
Contact:
Dr. John McEwan
Agresearch Invermay
Private Bag 50034
Mosgiel 9053
Dunedin
NEW ZEALAND
Tel: +64 +03 489 3809
john.mcewan@agresearch.co.nz
Species / Breed: Ovine (Dorset Romney cross)
Inheritance Pattern: Likely to be autosomal dominant
Macroscopic Phenotype: 8% increase in size of l. dorsi muscle in carriers.
Enzyme Analysis: –
Molecular Analysis: Carwell locus on chromosome 18, likely to be 2–6 cM telomeric of CSSM18 (marker linked to the callipyge trait).
Histology: –
Pathology: –
Comparative: –
References:
Nicoll G.B. et al., Genetic linkage of microsatellite markers to the Carwell locus for rib-eye muscling in sheep. Proc. VI World Conf. Genet. Appl. Lvst Prod. Armidale Australia, 1998. 26: 529–532.
000004 Fecundity (Inverdale)
Contact:
Dr. George Davis
Animal Production Unit
AgResearch Invermay
Private Bag 50034
Mosgiel 9053
Dunedin
NEW ZEALAND
Tel: +64 +03 489 3809
george.davis@agresearch.co.nz
Species / Breed: Ovine (originally Romney, but now in a number of breeds).
Inheritance Pattern: X-linked
Macroscopic Phenotype: Ewes heterozygous for the Inverdale mutation ovulate on average one extra follicle each cycle. Ewes homozygous for the mutation are infertile.
Enzyme Analysis: Likely that BMP15 protein is inactive.
Molecular Analysis: The FecXi mutation (Inverdale) has been mapped to an oocyte derived growth factor gene (BMP15) located on the X chromosome. The mutation results in an aspartic acid replacing a valine residue in a highly conserved region of the protein.
Histology: –
Pathology: In ewes homozygous for the mutation follicles do not develop past primary stage, tumour-like structures also observed on ovaries. Heterozygous ewes show less selective pressure on follicles for ovulation.
Comparative Features: Mutation is orthologous to human region Xp11.2–11.4.
References:
Jolly, R.D. et al., Genetic disorders of sheep in New Zealand: A review and perspective. NZ Vet. J., 2004. 52(2): 52–64.
McNatty, K.P. et al., Genetic mutations influencing ovulation rate in sheep. Reprod. Fertil. Dev., 2001. 13(7–8): 549–55.
Juengel, J.L. et al., Gene expression in abnormal ovarian structures of ewes homozygous for the inverdale prolificacy gene. Biol. Reprod., 2000. 62(6): 1467–78.
Galloway, S.M. et al., Mutations in an oocyte-derived growth factor gene (BMP15) cause increased ovulation rate and infertility in a dosage-sensitive manner. Nat. Genet., 2000. 25(3): 279–83.
000005 Fecundity (Hanna)
Contact:
Dr. George Davis
Animal Production Unit
AgResearch Invermay
Private Bag 50034
Mosgiel 9053
Dunedin
NEW ZEALAND
Tel: +64 +03 489 3809
george.davis@agresearch.co.nz
Species / Breed: Ovine
Inheritance Pattern: X-linked
Macroscopic Phenotype: Ewes heterozygous for the Hanna mutation ovulate on average one extra follicle each cycle. Ewes homozygous for the mutation are infertile.
Enzyme Analysis: –
Molecular Analysis: The FecXh mutation (Hanna) has been mapped to an oocyte derived growth factor gene (BMP15) located on the X chromosome. The mutation results in a premature stop codon.
Histology: –
Pathology: In ewes homozygous for the mutation, follicles do not develop past primary stage; heterozygous ewes show less selective pressure on follicles for ovulation.
Comparative Features: Mutation is orthologous to human region Xp11.2–11.5.
References:
McNatty, K.P. et al., Genetic mutations influencing ovulation rate in sheep. Reprod. Fertil. Dev., 2001. 13(7–8): 549–55.
Juengel, J.L. et al., Gene expression in abnormal ovarian structures of ewes homozygous for the inverdale prolificacy gene. Biol. Reprod., 2000. 62(6): 1467–78.
Galloway, S.M. et al., Mutations in an oocyte-derived growth factor gene (BMP15) cause increased ovulation rate and infertility in a dosage-sensitive manner. Nat. Genet., 2000. 25(3): 279–83.
000006 Fecundity (Booroola)
Contact:
Dr. George Davis
Animal Production Unit
AgResearch Invermay
Private Bag 50034
Mosgiel 9053
Dunedin
NEW ZEALAND
Tel: +64 +03 489 3809
george.davis@agresearch.co.nz
Species / Breed: Ovine
Inheritance Pattern: Autosomal recessive
Macroscopic Phenotype: Ewes heterozygous for the Booroola mutation have an ovulation rate of 3–4; ewes homozygous for the mutation have an ovulation rate of 5–14 (where a wild type ovulation rate is 1–2).
Enzyme Analysis: –
Molecular Analysis: The FecB (Booroola) mutation has been mapped to sheep chromosome 6q23-31 and is a point mutation in a highly conserved region of the MBPR-1B gene (a receptor for BMP-1B).
Histology: –
Pathology: BMPR-1B mRNA is not localised purely to the ovary, it is therefore suggested that the mutation affects ovulation through extra-ovarian actions.
Comparative Features: –
References:
Wilson, T. et al., Highly prolific Booroola sheep have a mutation in the intracellular kinase domain of bone morphogenetic protein IB receptor (ALK-6) that is expressed in both oocytes and granulosa cells. Biol. Reprod., 2001. 64(4): 1225–35.
McNatty, K.P. et al., Genetic mutations influencing ovulation rate in sheep. Reprod. Fertil. Dev., 2001. 13(7–8): 549–55.
000007 Fecundity (Woodlands)
Contact:
Dr. George Davis
Animal Production Unit
AgResearch Invermay
Private Bag 50034
Mosgiel 9053
Dunedin
NEW ZEALAND
Tel: +64 +03 489 3809
george.davis@agresearch.co.nz
Species / Breed: Ovine
Inheritance Pattern: X-linked, maternally imprinted
Macroscopic Phenotype: Ewes heterozygous for the Woodlands mutation have a 20–40% higher ovulation rate than wild type. No homozygotes for the mutation have been recorded yet.
Enzyme Analysis: –
Molecular Analysis: Inheritance patterns indicate the FeX2w (Woodlands) mutation is on the X-chromosome, however the location is unclear. Pedigree information shows maternal imprinting of the mutation.
Histology: –
Pathology: The mechanism by which the Woodlands mutation increases ovulation rate is unclear.
Comparative Features: –
References:
Davis, G.H. et al., Evidence that an imprinted gene on the X chromosome increases ovulation rate in sheep. Biol. Reprod., 2001. 64(1): 216–21.
McNatty, K.P. et al., Genetic mutations influencing ovulation rate in sheep. Reprod. Fertil. Dev., 2001. 13(7–8): 549–55.
000008 Cystic Fibrosis
Contact:
Dr. Diana Hill
c/o Dr. John McEwan
Agresearch Invermay
Private Bag 50034
Mosgiel 9053
Dunedin
NEW ZEALAND
Tel: +64 +03 489 3809
john.mcewan@agresearch.co.nz
Species / Breed: Ovine
Inheritance Pattern: Autosomal recessive
Macroscopic Phenotype: –
Enzyme Analysis: CF sheep tested for pancreatic enzyme function however results were inconclusive.
Molecular Analysis: Missense mutation in exon 7 of ovine CFTR gene.
Histology: –
Pathology: –
Comparative Features: Mutation is identical to a CF causing mutation (R297Q) in humans.
References:
Tebbutt, S.J. et al., Genetic variation within the ovine cystic fibrosis transmembrane conductance regulator gene. Mutat. Res., 1998. 382(3–4): 93–8.
Tebbutt, S.J. et al., Molecular analysis of the ovine cystic fibrosis transmembrane conductance regulator gene. Proc. Natl Acad. Sci. USA, 1995. 92(6): 2293–7.
000009 Cataracts
Contact:
Dr. Jim Morton
Lincoln University
Agriculture and Life Sciences Division
PO Box 84
Canterbury
NEW ZEALAND
Tel: +64 +03 325 2811
mortonj@lincoln.ac.nz
Species / Breed: Ovine (Coopworth)
Inheritance Pattern: Autosomal dominant
Macroscopic Phenotype: Cloudiness of lens. Blindness.
Enzyme Analysis: Increased levels of calcium dependent protease (calpain).
Molecular Analysis: –
Histology: Accumulation of insoluble protein.
Pathology: Increased calpain levels cause break down of lens proteins.
Comparative Features: Similar developmental process in humans.
References:
Jolly, R.D. et al., Genetic disorders of sheep in New Zealand: A review and perspective. NZ Vet. J., 2004. 52(2): 52–64.
Brooks, H.V. et al., An inherited cataract in New Zealand Romney sheep. NZ Vet. J., 1982. 30(8): 113–4.
000010 Low Bone Density
Contact:
Dr. Anna Campbell
c/o Dr. John McEwan
Agresearch Invermay
Private Bag 50034
Mosgiel 9053
Dunedin
NEW ZEALAND
Tel: +64 +03 489 3809
john.mcewan@agresearch.co.nz
Species / Breed: Ovine (Coopworth)
Inheritance Pattern: QTL
Macroscopic Phenotype: Low bone density correlated with lean muscle.
Enzyme Analysis: –
Molecular Analysis: Genotyped for 138 markers. 9 QTLs found with markers on chromosome 1p and 24 (for long and flat bones, respectively) being noted as significant.
Histology: –
Pathology: –
Comparative Features: A number of the BD QTLs identified in sheep are in equivalent chromosomal positions in humans, such as the chromosome 1p QTL in sheep which also lies in the 1p region in humans. Bone development process in humans is also similar to that of sheep.
References:
Campbell, A.W. et al., Bone density in sheep: genetic variation and quantitative trait loci localisation. Bone, 2003. 33(4): 540–8.
Morris, C.A. et al., Selection for high or low backfat depth in Coopworth sheep: juvenile traits. Anim. Sci., 1997. 65: 93–103.
000011 Mucopolysaccharidosis IIIa (Sanfilippo syndrome)
Contact:
Professor Robert D. Jolly (Emeritus)
Massey University
Institute of Veterinary, Animal and Biological Sciences
Private Bag 11 222
Palmerston North
NEW ZEALAND
Tel: +64 +06 356 9099
R.D.Jolly@massey.ac.nz
Species / Breed: Canine (Huntaway)
Inheritance Pattern: Autosomal recessive
Macroscopic Phenotype: Progressive ataxia and hypermetria of all four limbs.
Enzyme Analysis: Deficiency of heparan sulfate sulfamidase (SGSH).
Molecular Analysis: Insertion of an adenosine at position 708–709 (708–709insA) of the SGSH cDNA sequence.
Histology: Ganglioside accumulation in neurons, vacuolated macrophages in perivascular spaces and leptomeninges, vacuolated hepatocytes and fibroblasts.
Pathology: Widespread lesions of central nervous system
Comparative Features: Analogous to Sanfilippo syndrome in children.
References:
Jolly, R.D. et al., Screening for the Mucopolysaccharidosis-IIIA gene in Huntaway dogs. NZ Vet. J. 2002. 50(3): 122.
Yogalingam, G. et al., Identification of a mutation causing mucopolysaccharidosis type IIIA in New Zealand Huntaway dogs. Genomics, 2002. 79(2): 150–3.
Jolly, R.D. et al., An histological diagnosis of mucopolysaccharidosis IIIA in an English wire haired Daschund. Vet. Rec., 2001. 148: 564–7.
Jolly, R.D. et al., Mucopolysaccharidosis IIIA (Sanfilippo syndrome) in a New Zealand Huntaway dog with ataxia. NZ Vet. J., 2000. 48(5): 144–8.
Jolly, R.D. and Walkley S.U., Lysosomal storage diseases of animals: an essay in comparative pathology. Vet. Pathol., 1997. 34: 527–48.
000012 Myophosphorylase deficiency (Glycogen storage disease type V)
Contact:
Professor Robert D. Jolly (Emeritus)
Massey University
Institute of Veterinary, Animal and Biological Sciences
Private Bag 11 222
Palmerston North
NEW ZEALAND
Tel: +64 +06 356 9099
R.D.Jolly@massey.ac.nz
Species / Breed: Bovine (Charolais)
Inheritance Pattern: Autosomal recessive
Macroscopic Phenotype: Recumbency following forced exercise.
Enzyme Analysis: Inability to mobilise glucose stored from muscle glycogen due to inactive myophosphorylase.
Molecular Analysis: Missense mutation in codon 489 of myophosphorylase gene.
Histology: –
Pathology: Severe rhabdomyolysis, dehydration and electrolyte imbalance.
Comparative Features: Analogous to human glycogen storage disease type V.
References:
Johnstone, A.C. et al., Myophosphorylase deficiency (Glycogen storage disease type V) in a herd of Charolais cattle in New Zealand: confirmation by PCR-RFLP testing. NZ Vet. J., 2004. 52(6): 404–8.
Tsujino, S. et al., Cloning of bovine muscle glycogen phosphorylase cDNA and identification of a mutation in cattle with myophosphorylase deficiency, an animal model for McArdle's disease. Neuromuscular Disorders, 1996. 6: 19–26.
000013 Chondrodysplasia (Dwarfism, Spider syndrome)
Contact:
Professor Keith Thompson
Massey University
Institute of Veterinary, Animal and Biological Sciences
Private Bag 11 222
Palmerston North
NEW ZEALAND
Tel: +64 +06 356 9099
K.G.Thompson@massey.ac.nz
Species / Breed: Ovine (Texel)
Inheritance Pattern: Autosomal recessive (?)
Macroscopic Phenotype: Reduced growth rate, shortened neck and legs, various forelimb deformities and a progressive resistance to walk.
Enzyme Analysis: –
Molecular Analysis: –
Histology: Disorganisation of chondrocytes in articular and physeal cartilage. Chondroid matrix surrounding chondrocytes has an abnormal fibrillar appearance.
Pathology: Extensive loss of articular cartilage and exposure of subchondral bone on weight bearing surfaces (such as the proximal surfaces of humeri and femurs).
Comparative Features: Similar to certain types of chondroplaysia and dysplasia in humans.
References:
Jolly, R.D. et al., Genetic disorders of sheep in New Zealand: A review and perspective. NZ Vet. J., 2004. 52(2): 52–64.
Thompson, K.G. et al., Chondrodysplasia of Texel sheep – a new disease of suspected genetic aetiology. NZ Vet. J., 2003. 51(1): 45–6.
West, D.M. et al., Hereditary chondrodysplasia (“spider syndrome”) in a New Zealand Suffolk lamb of American origin. NZ Vet. J., 1995. 43(3): 118–22.
000014 Glycogen storage disease type II (Pompe disease)
Contact:
Professor Robert D. Jolly (Emeritus)
Massey University
Institute of Veterinary, Animal and Biological Sciences
Private Bag 11 222
Palmerston North
NEW ZEALAND
Tel: +64 +06 356 9099
R.D.Jolly@massey.ac.nz
Species / Breed: Ovine (Merino)
Inheritance Pattern: Autosomal recessive
Macroscopic Phenotype: Incoordination, lethargy and muscle weakness.
Enzyme Analysis: Deficiency of acidic alpha-glucosidase.
Molecular Analysis: –
Histology: Build up of glycogen in neurons, skeletal, smooth and cardiac muscle cells.
Pathology: –
Comparative Features: Similar to Pompe's disease in humans.
References:
Jolly, R.D. et al., Genetic disorders of sheep in New Zealand: A review and perspective. NZ Vet. J., 2004. 52(2): 52–64.
Jolly, R.D. and Walkley, S.U., Lysosomal storage diseases of animals: an essay in comparative pathology. Vet. Pathol., 1997. 34: 527–48.
Manktelow, B.W. and Hartley, W.J., Generalized glycogen storage disease in sheep. J. Comp. Pathol., 1975. 85(1): 139–45.
000015 Lower Motor Neuron Disease
Contact:
Dr. Kathleen Parton
Massey University
Institute of Veterinary, Animal and Biomedical Sciences (IVABS) PN 412
Private Bag 11 222
Palmerston North
NEW ZEALAND
Tel: + 64 +06 356 9099
K.Parton@massey.ac.nz
Species / Breed: Ovine (Open Face Romney)
Inheritance Pattern: Autosomal recessive
Macroscopic Phenotype: Progressive weakness and ataxia. Premature death.
Enzyme Analysis: Condition is characterised in humans and cattle as a deficiency of survival motor neuron1 (SMN1) protein.
Molecular Analysis: The gene for SMN1 has been mapped to cattle chromosome 20, equivalent to sheep chromosome 16. However, it has not yet been mapped in sheep.
Histology: Spheroids seen in pons, cervical and thoracic ventral horns. Wallerian degeneration prominent within the brachial and femoral nerves and nerve branches within the skeletal muscle.
Pathology: If lambs are raised artificially past initial clinical signs, wasting and paleness of the skeletal muscles is evident.
Comparative Features: Similar to spinal muscular atrophy in humans and cattle.
References:
Jolly, R.D. et al., Genetic disorders of sheep in New Zealand: A review and perspective. NZ Vet. J., 2004. 52(2): 52–64.
Anderson, P.D. et al., A lower motor neuron disease in newborn Romney lambs. NZ Vet. J., 1999. 47(3): 112–4.
000016 Neuroaxonal dystrophy
Contact:
Professor Robert D. Jolly (Emeritus)
Massey University
Institute of Veterinary, Animal and Biological Sciences
Private Bag 11 222
Palmerston North
NEW ZEALAND
Tel: +64 +06 356 9099
R.D.Jolly@massey.ac.nz
Species / Breed: Ovine (Coopworth)
Inheritance Pattern: Autosomal recessive
Macroscopic Phenotype: Progressive ataxia with eventual collapse of hindquarters and premature death.
Enzyme Analysis: –
Molecular Analysis: –
Histology: Spheroidal swelling of axons due to accumulation of axoplasmic organelles. Prominent in proximal or distal entities but can be seen along length.
Pathology: Result of a non-specific reaction of the neurons to a variety of stimuli including toxic substances and genetic factors.
Comparative Features: Axonal swellings have been reported in a number of different species, including humans.
References:
Jolly, R.D. et al., Genetic disorders of sheep in New Zealand: A review and perspective. NZ Vet. J., 2004. 52(2): 52–64.
Harper, P. and Morton, A.G., Neuroaxonal dystrophy in merino sheep. Australian Vet. J., 1991. 68: 152–3.
Nuttal, W.O., Ovine neuroaxonal dystrophy in New Zealand. NZ Vet. J., 1988. 36(1): 5–7.
000017 Neuronal ceroid lipofuscinosis (variant CLN6, late infantile)
Contact:
Professor David Palmer
Agriculture and Life Sciences Division
PO Box 84
Lincoln University
Lincoln 7647
Canterbury
NEW ZEALAND
Tel: +64 +03 325 2811
E-mail: Palmerd@lincoln.ac.nz
Species / Breed: Ovine (South Hampshire)
Inheritance Pattern: Autosomal recessive
Macroscopic Phenotype: Progressive blindness from 7–10 months, abnormal behaviour, partial seizures located around the head region, motor disturbances and premature death
Enzyme Analysis: Accumulation of mitochondrial ATP synthase subunit c
Molecular Analysis: Mapped to sheep chromosome 7q13-15
Histology: Neuron loss in central nervous system and accumulation of fluorescent lipopigment and mitochondrial ATP synthase subunit c in cytoplasmic inclusions of remaining neurons.
Pathology: Atrophic lesions of cerebral cortex, especially the optic cortex, and retinal atrophy.
Comparative: Histologicaly and pathologically similar to the human variant CLN6. Chromosomal location of human CLN6 (15q21-23) is systemic to the region mapped to sheep chromosome 7.
References:
Jolly, R.D. et al., Genetic disorders of sheep in New Zealand: A review and perspective. NZ Vet. J., 2004. 52(2): 52–64.
Palmer, D.N., Learning from an animal equivalent of a human neurodegenerative disease: Batten disease in sheep. Proceedings of the 2003 conference for the Australia and New Zealand Council for the Care of Animals in Research and Teaching. Christchurch, 2003.
Kay, G.W., S.M. Hughes, and Palmer, D.N., In vitro culture of neurons from sheep with Batten disease. Mol. Genet. Metab., 1999. 67(1): 83–8.
Hughes, S.M. et al., Disease-specific pathology in neurons cultured from sheep affected with ceroid lipofuscinosis. Mol. Genet. Metab., 1999. 66(4): 381–6.
Broom, M.F., Zhou, C., and Hill, D.F., Progress toward positional cloning of ovine neuronal ceroid lipofuscinosis, a model of the human late-infantile variant CLN6. Mol. Genet. Metab., 1999. 66(4): 373–5.
Broom, M.F. et al., Ovine neuronal ceroid lipofuscinosis: a large animal model syntenic with the human neuronal ceroid lipofuscinosis variant CLN6. J. Med. Genet., 1998. 35(9): 717–21.
Jolly, R.D. and Walkley, S.U., Lysosomal storage diseases of animals: an essay in comparative pathology. Vet. Pathol., 1997. 34: 527–48.
Jolly, R.D., Comparative biology of the neuronal ceroid-lipofuscinoses (NCL): an overview. Am. J. Med. Genet., 1995. 57(2): 307–11.
Jolly, R.D. and Palmer, D.N., The neuronal ceroid-lipofuscinoses (Batten disease): comparative aspects. Neuropathol. Appl. Neurobiol., 1995. 21(1): 50–60.
Jolly, R.D., Martinus, R.D, and Palmer, D.N., Sheep and other animals with ceroid-lipofuscinoses: their relevance to Batten disease. Am. J. Med. Genet., 1992. 42(4): 609–14.
000018 Neuronal ceroid lipofuscinosis (exact variant undetermined; similar to late infantile variants)
Contact:
Professor David Palmer
Agriculture and Life Sciences Division
PO Box 84
Lincoln University
Lincoln 7647
Canterbury
NEW ZEALAND
Tel: +64 +03 325 2811
E-mail: Palmerd@lincoln.ac.nz
Species / Breed: Ovine (Borderdale)
Inheritance Pattern: Autosomal recessive
Macroscopic Phenotype: Progressive blindness and abnormal behaviour.
Enzyme Analysis: Accumulation of mitochondrial ATP synthase subunit c.
Molecular Analysis: A silent substitution mutation has been found in exon 7 of the CLN6 gene (A/G) linked to the mutation currently being searched for.
Histology: Neuron loss in central nervous system and accumulation of fluorescent lipopigment and mitochondrial ATP synthase subunit c in cytoplasmic inclusions of remaining neurons. Ultrastructure of inclusions differs in shape (curvilinear profile) from that of CLN6 variant.
Pathology: More severe brain atrophy than CLN6 variant.
Comparative: Resembles other neuronal ceroid lipofuscinoses (NCLs); however, is probably a different variant caused by a different mutation.
References:
Jolly, R.D. et al., Genetic disorders of sheep in New Zealand: A review and perspective. NZ Vet. J., 2004. 52(2): 52–64.
Palmer, D.N., Learning from an animal equivalent of a human neurodegenerative disease: Batten disease in sheep. Proceedings of the 2003 Conference for the Australia and New Zealand Council for the Care of Animals in Research and Teaching. Christchurch, 2003.
Jolly, R.D. et al., Neuronal ceroid lipofuscinosis in Borderdale sheep. NZ Vet. J., 2002. 50(5): 199–202.
Jolly, R.D., Comparative biology of the neuronal ceroid-lipofuscinoses (NCL): an overview. Am. J. Med. Genet., 1995. 57(2): 307–11.
Jolly, R.D. and Palmer, D.N., The neuronal ceroid-lipofuscinoses (Batten disease): comparative aspects. Neuropathol. Appl. Neurobiol., 1995. 21(1): 50–60.
000019 Neuronal ceroid lipofuscinosis (variant CLN6, late infantile)
Contact:
Professor David Palmer
Agriculture and Life Sciences Division
PO Box 84
Lincoln University
Lincoln 7647
Canterbury
NEW ZEALAND
Tel: +64 +03 325 2811
E-mail: Palmerd@lincoln.ac.nz
Species / Breed: Ovine (South Hampshire x Coopworth); Chimera
Inheritance Pattern: –
Macroscopic Phenotype: Chimera of an affected (CLN6 varient) South Hampshire ewe and a normal Coopworth ram. Lambs display visible phenotypes (e.g., coat colour) of both parents.
Enzyme Analysis: –
Molecular Analysis: –
Histology: –
Pathology: –
Comparative: –
References:
Palmer, D.N., Learning from an animal equivalent of a human neurodegenerative disease: Batten disease in sheep. Proceedings of the 2003 Conference for the Australia and New Zealand Council for the Care of Animals in Research and Teaching. RSNZ, Christchurch, 2003.
000020 Alpha Mannosidosis
Contact:
Professor Robert D. Jolly (Emeritus)
Massey University
Institute of Veterinary, Animal and Biological Sciences
Private Bag 11 222
Palmerston North
NEW ZEALAND
Tel: +64 +06 356 9099
E-mail: R.D.Jolly@massey.ac.nz
Species / Breed: Bovine (Angus and Murray Grey)
Inheritance Pattern: Autosomal recessive
Macroscopic Phenotype: Ataxia, incoordination, head tremors, aggressive tendency and premature death.
Enzyme Analysis: Defficiency of lysosomal alpha-mannosidase. Enzymatic screening programs established and used extensively in the past.
Molecular Analysis: T916C transition mutation in bovine alpha-mannosidase gene identified for Angus and Murray Grey breeds, different mutations identified for different breeds. PCR tests developed and screening programs implemented.
Histology: Vacuolation of macrophages in lymph nodes, pancreatic exocrine cells and neurons. Accumulation of a mannose/glucosamine oligosaccharide.
Pathology: –
Comparative Features: Similar to human alpha-mannosidosis in regard to pathology and the nature of the storage substance and enzyme defficiency. Mutation for the human form has been mapped to human chromosome 19p13.2-q12.
References:
Jolly, R.D., and Walkley, S.U., Lysosomal storage diseases of animals: an essay in comparative pathology. Vet. Pathol., 1997. 34: 527–48.
Jolly, R.D., Mannosidosis and its control in Angus and Murray Grey cattle. NZ Vet. J., 1978. 26(8): 194–8.
Jolly, R.D., Animal model of human disease: mannosidosis of children, other inherited lysosomal storage diseases. Am. J. Pathol., 1974. 74(1): p. 211–4.
000021 Polycystic kidney disease (ARPKD)
Contact:
Professor Michael Eccles
Otago University
Department of Pathology
PO Box 913m
Dunedin
NEW ZEALAND
Tel: +64 +03 479 7138
E-mail: michael.eccles@stonebow.otago.ac.nz
Species / Breed: Ovine (Coopworth)
Inheritance Pattern: Likely to be autosomal recessive.
Macroscopic Phenotype: Lambs stillborn with severely enlarged kidneys.
Histology: –
Pathology: Multiple renal cysts and biliary dysplasia.
Comparative: Model for human ARPKD which is linked to a mutation in human chromosome region 6p21-cen. This mutation is being used for a candidate mutation search in sheep.
References:
Jolly, R.D. et al., Genetic disorders of sheep in New Zealand: A review and perspective. NZ Vet. J., 2004. 52(2): 52–64.
000022 Polycystic kidney disease (ARPKD)
Contact:
Professor Robert D. Jolly (Emeritus)
Massey University
Institute of Veterinary, Animal and Biological Sciences
Private Bag 11 222
Palmerston North
NEW ZEALAND
Tel: +64 +06 356 9099
E-mail: R.D.Jolly@massey.ac.nz
Species / Breed: Ovine
Inheritance Pattern: Autosomal recessive
Macroscopic Phenotype: Lambs born dead with severely enlarged kidneys.
Enzyme Analysis: –
Molecular Analysis: –
Histology: –
Pathology: Multiple renal cysts and biliary dysplasia; different mutation from polycystic kidney disease model (000021).
Comparative Features: Similar to ARPKD in children.
References:
Jolly, R.D. et al., Genetic disorders of sheep in New Zealand: A review and perspective. NZ Vet. J., 2004. 52(2): 52–64.
000023 Epidermolysis bullosa simplex (EB)
Contact:
Dr Russell Snell
ViaLactia Biosciences
PO Box 109185
Newmarket
Auckland 1031
NEW ZEALAND
Tel: +64 +09 921 2760
E-mail: russell.snell@vialactia.com
Species / Breed: Bovine
Inheritance Pattern: Autosomal dominant
Macroscopic Phenotype: Loss of skin and mucosa from contact areas and inflammation. Examination of skin samples under light microscopy reveals separation of the epidermis from the dermis.
Enzyme Analysis: –
Molecular Analysis: Mutation in keratin 5. Sequencing has identified a G to A substitution in all affected animals leading to an amino acid change of glutamic acid to lysine in the final E (478) of the KLLEGE motif of the protein.
Histology: Light microscopic examination of skin sections has revealed clefts in the sub-basilar (subepithelial) zone and the suprabasilar zones.
Pathology: See publications for details.
Comparative Features: Equivalent to human EB; the same mutation has previously been described in EB simplex in humans.