Symbol Targeted Gene Phenotype details References Ref.

ID Map
Pos.
Ags alpha galactosidase clinically normal at 10 weeks, complete absence of alpha- Ohshima et al. (1997) PNAS USA 94: 2540-2544 J:39394 53.0
Gal A activity, examination of liver and kidney revealed
similar pathophysiology to human Fabry disease
Agtr2 angiotensin II receptor, blood pressure increase, increased sensitivity to pressor Hein et al. (1995) Nature 377: 744-747; J:29456 12.5
type 2 action of angiotensin II, lowered body temperature and Ichiki et al. (1995) Nature 377: 748-750 J:29457
reduced exploratory behaviour

Aldgh X-linked reduced beta-oxidation of very long chain fatty acids Lu et al. (1997) PNAS USA 94: 9366-9371; J:42479 29.5
adrenoleukodystrophy (VLCFAs) with consequent elevation of saturated VLCFAs in ForssPetter et al. (1997) J. Neurosci. Res. 50: 829- J:44812
total lipids of all tissues and cholesterol esters in 843
adrenocortical cells, but no neurological involvement seen in
mice up to 6 months

Bgn biglycan skeletal phenotype marked by progressive lowering of bone Xu et al.(1998) Nature Genetics 20: 78-82 J:49647 29.3
mass, suggested model for role of ECM proteins in
osteoporosis

Brs3 bombesin receptor mild obesity, hypertension, impaired glucose metabolism, Ohki-Hamazaki et al. (1997) Nature 390: 165-169 J:44242
subtype-3 reduced metabolic rate, increased feeding efficiency and
subsequent hyperphagia

Btk Bruton mild X-linked immunodeficiency, with additional compromise Kerner et al. (1995) Immunity 3: 301-312; J:28967 51.0
agammaglobulinemia of B cell precursor expansion Khan et al. (1997) Int. Immunol. 9: 395-405 Medline
97244169
tyrosine kinase(=xid)
Cd40l CD40 antigen ligand failure to undergo isotype switching to T-cell-dependent Castigli et al. (1995) Int. Arch. Allergy Immunol. 107: Medline 18.0
antigens, normal response to T-cell-independent antigens 37-39; Xu et al. (1994) Immunity 1: 423-231; 95337793
Renshaw et al. (1994) J. Exp. Med. 180: 1880-1900. J:25010
J:21137
Cf8 coagulation factor VIII <1% factor VIII clotting activity, significant bleeding after tail Bi et al. (1995) Nature Genetics 10: 119-121 J:24941 30.5
biopsy which may be lethal, no spontaneous bleeding
Cf9 coagulation factor IX absence of factor IX antigen in plasma, <5% factor IX Wang et al. (1997) PNAS USA 94: 11563-11566 J:43590 22.0
clotting activity

Cybb subunit of NADPH- chronic granulomatous disease(CGD), lack phagocyte Pollock et al. (1995) Nature Genetics 9: 202-209; J:22868 2.8
oxidase complex superoxide production, increased susceptibility to infection Morgenstern et al. (1997) J. Exp. Med. 185: 207-218 Medline
and altered inflammatory response to thioglycollate 97169063
peritonitis

Dmd dystrophin, muscular hypertrophic skeletal muscles, fibre size variations with Araki et al. (1997) Biochem. Biophys. Res. Comm. J:43164 32.0
dystrophy necrosis and regeneration 238: 492-497

Cask Ca2+ dependent cleft secondary palate, neonatal male lethality, suggested Wilson et al. (1993) Cell Growth & Diff. 4: 67-76; J:18214 5.0
protein kinase model for human X-linked cleft secondary palate syndrome Laverty and Wilson (1998)
Genomics 53: 29-41
Fmr1 fragile X mental Macroorchidism, learning deficits, hyperactivity and lack of Bakker et al. (1994) Cell 78: 23-33; J:19220 24.5
retardation syndrome 1 normal Fmr1 protein Oostra and Hoogeveen et al. (1997) Annals of J:47489
Medicine 29: 563-567
homologue
G6pdx glucose-6-phosphate at ES cell level only, clones with undetectable levels of the Pandolfi et al. (1995) EMBO J. 14: 5209-5215 Medline 30.02
dehydrogenase enzyme are extremely sensitive to hydrogen peroxide and 96080156
diamide

Gata1 GATA-binding protein male neonatal lethal, mid-gestation embryos pallid with Pevny et al. (19910 Nature 349: 257-260; Fujiwara et J:36462 2.1
1 arrest of erythroid development al. (1996) PNAS USA 93: 12355-12358; J:36249
Takahashi et al. (1997) J. Biol. Chem. 272: 12611- J:40321
12615
Gjb1 gap junction protein from 3 months progressive demyelinating neuropathy, motor Scherer et al. (1998) Glia 24: 8-20 Medline 38.0
connexin32 fibres more affected than sensory fibres, model for Charcot- 98365842
Marie-Tooth disease?

Gpc3 glypican 3 Li et al. (1998) Clin. Genet. 53: 165-170 J:47826 syntenic

Grpr gastrin releasing no gross phenotypic abnormalities, but bombesin ineffective Hampton et al. (1998) PNAS USA 95: 3188-3192 J:46897 70.0
peptide receptor at suppress glucose intake

Gyk glycerol kinase males normal at birth but exhibit growth retardation, altered Huq et al. (1997) Hum. Mol. Genet. 11: 1803-1809 J:43449 33.0
fat metabolism with profound hypoglycerolemia and elevated
free fatty acids, autonomous glucocorticoid synthesis and
death by 3-4 days. Heterozygous females are healthy and
biochemically normal
Hprt hypoxanthine none unless Aprt also eliminated (Wu and Melton (1993) Hooper et al. (1987) Nature 326: 292-295; J:15483 17.0
phosphoribosyl- Nature Genet. 3: 235-240) Kuehn et al. (1987) Nature 326: 295-298; J:15485
Nehls et al. (1994) Biotechniques 17: 770-775; Medline
transferase Tsuda et al. (1997) Genomics 42:413-421 95134423
J:41459
Htr2c 5-hydroxytryptamine overweight because of abnormal feeding behaviour, Tecott et al. (1995) Nature 374: 542-546 J:24339 66.15
(serotonin) receptor 2C spontaneous death from seizures

Il2rg interleukin 2 receptor, similar phenotype to human XSCID, decrease in lymphocyte Leonard et al. (1995) Immunol. Rev. 148: 97-114; Medline 38.0
gamma chain numbers but increase in monocytes, few T cells in young Sugamura et al. (1996) Ann. Rev. Immunol. 14: 179- 96422667
mice and no natural killer cells 205; Medline
Ohbo et al. (1996) Blood 87: 956-967 96292426
J:31167
L1cam L1 cell adhesion smaller than wild type animals, uncoordinated hind legs, Dahme et al. (1997) Nature Genetics 17: 346-349; J:43838 29.51
molecule hypoplasia of corticospinal tract, abnormal brain pathology, Fransen et al. (1998) Hum. Mol. Genet. 7: 999-1009 J:47995
and impaired exploratory behaviour

Maoa monoamine oxidase a pups had elevated serotonin levels, trembling, difficulty in Cases et al. (1995) Science 268: 1763-1766 J:26232 5.2
righting and fearfulness, adults had distinct behavioural
syndrome with enhanced aggression in males
Maob monoamine oxidase b increased reactivity to stress, increased levels of beta- Grimsby et al. (1997) Nature Genetics 17: 206-210 J:43648 5.2
phenylethylamine, resistance to neurodegenerative effects of
MPTP toxin (which induces a Parkinson's like condition)
Mecp2 methyl CpG binding chimareic embryos exhibited developmental defects with Tate et al. (1996) Nature Genetics 12: 205-208 J:31573 29.6
protein 2 severity proportional to mutant cell contributions
Mpp1 murine p55 meeting abstract Kim et al. (1996) Mol. Biol. of the Cell 7: 999 IS 1059- 30.48
1524
Ndph Norrie disease development of retrolental structures in vitreous body, Berger et al. (1996) Hum. Mol. Genet. 5: 51-59 J:30902 5.3
homologue disorganisation of retinal ganglion cell layer, occasional loss
of outer plexiform layer with resultant interchange of
inner/outer nuclear layer, absence of outer segments of
photoreceptor cell layer

Ocrl oculocerebrorenal no abnormal phenotype, with postulated compensation by Janne et al. (1998) J. Clin. Invest. 101: 2042-2053 J:47884 syntenic
syndrome of Lowe the autosomal gene inositol polyphosphate 5-phosphatase
(Inpp5b) as explanation

Piga phosphatidylinositol wrinkled and scaly skin, death a few days after birth Tarutani et al. (1997) PNAS USA 94: 7400-7405 J:41746 67.0
glycan, class A

Plp myelin proteolipid no gross effect, assembly and maintenance of normal Boison and Stoffel (1994) PNAS USA 91: 11709- J:21976 56.0
protein(=DXNds2, amounts of myelin, progressive tract-specific axonopathy 11713; Griffiths et al. (1995) Brain Pathol. 5: 275- J:31051
notes: (1) correction of natural mutant with wild type 281; J:38856
DXMit9, jimpy) transgene not possible (2) over expression has more severe Klugmann et al. (1997) Neuron 18: 59-70; Medline
clinical effects Griffiths et al. (1998) Microsc. Res. Tech. 41: 344- 98336162
358

Pou3f4 Pou domain, class 3, vertical head bobbing and hearing loss, dysplastic bony Crenshaw et al.( 1998) Heredity Deafness Newsletter J:32903 49.0
transcription factor 4 compartment of the inner ear 15: 46; Ikeda et al. (1998) Heredity Deafness J:48665
Newsletter 15: 47-48

Pou4f2 POU domain,class 4, selective loss of 70% of retinal ganglion cells, but other Gan et al. (1996) PNAS USA 93: 3920-3925; syntenic
transcription factor 2 neurons in the retina and brain essentially unaffected Erkman et al. (1996) Nature 381: 603-606

Rep1 Rab escort protein 1, embryonic male lethal; heterozygous females and chimeras van den Hurk et al (1997) Hum. Mol. Genet. 6: 851- J:40673 syntenic
(mutated in have a variable number of photoreceptor cells 858
choroideraemia)
Syn1 synapsin 1 no gross abnormalities, mossy fibre giant terminals reduced, Rosahl et al. (1993) Cell 75: 661-670; J:15701 6.2
fewer synaptic vesicles, and presynaptic structures altered Takei et al. (1995) J. Cell Bio. 131: 1789-1800 J:30400
Syp synaptophysin indistinguishable from normal littermates, predendritic Arrandale et al. (1996) J. Biol. Chem. 271: 21353- J:35137; 1.7
neurites and axon outgrowth retarded in hippocampal 21358; Chin et al. (1995) PNAS USA 92: 9230-9234; J:29085
neurons, with delayed synapse formation; homozygotes die Eshkind and Leube (1995) Cell Tissue Res. 282: J:30488
prior to 10.5 dpc 423-433; J:33035
McMahon et al. (1996) PNAS USA 93: 4760-4764
Timp tissue inhibitor of no effect on steroidogenesis, reduced ovarian TIMP2 and Nothnick et al. (1997) Bio. Reprod. 56: 1181-1188; J; 40265 M 6.2
metalloproteinase TIMP3, at ES cell level only, more invasive than normal cells Alexander and Werb (1992) J. Cell Biol. 118: 727-
739
Wasp Wiskott-Aldrich decreased peripheral blood lymphocyte and platelet Snapper et al. (1998) Immunity 9: 81-91 J:48836 2.1
syndrome protein numbers, chronic colitis

Xist inactive X specific mutant males inaffected, females inheriting mutant paternal Marahens et al. (1997) Genes Dev. 11: 156-166 J:38094 42.0
transcripts X chromosome severely retarded and die in utero

Xnp X-linked nuclear at cellular level, increased sensitivity to ionising radiation, Essers et al. (1997) Cell 89: 195-204 J:39642 43.8
protein mitomycin C and methyl methanesulphonate

male and female mutants smaller. with lowere viability and

X-linked zinc finger fewer germ cells, hemizygotes had reduced sperm count
Zfx protein and homozygotes a reduced number of oocytes Luoh et al. (1997) 124: 22275-2284 J:41131 34.6
 Different ref. format

TARGETED DISRUPTION OF X-LINKED G

Symbol Targeted Gene Phenotype details

Ags alpha galactosidase clinically normal at 10 weeks, complete absence of alpha-Gal

A activity, examination of liver and kidney revealed similar
pathophysiology to human Fabry disease
Agtr2 angiotensin II receptor, blood pressure increase, increased sensitivity to pressor action
type 2 of angiotensin II, lowered body temperature and reduced
exploratory behaviour
Aldgh X-linked reduced beta-oxidation of very long chain fatty acids (VLCFAs)
adrenoleukodystrophy with consequent elevation of saturated VLCFAs in total lipids
of all tissues and cholesterol esters in adrenocortical cells, but
no neurological involvement seen in mice up to 6 months

Bgn biglycan skeletal phenotype marked by progressive lowering of bone

mass, suggested model for role of ECM proteins in
osteoporosis
Brs3 bombesin receptor mild obesity, hypertension, impaired glucose metabolism,
subtype-3 reduced metabolic rate, increased feeding efficiency and
subsequent hyperphagia

Btk Bruton mild X-linked immunodeficiency, with additional compromise of

agammaglobulinemia B cell precursor expansion
tyrosine kinase(=xid)

Cd40l CD40 antigen ligand failure to undergo isotype switching to T-cell-dependent

antigens, normal response to T-cell-independent antigens
Cf8 coagulation factor VIII
Cf9 coagulation factor IX absence of factor IX antigen in plasma, model for haemophilia
B
Chm mouse Choroideremia embryonic male lethal

Cybb subunit of NADPH- chronic granulomatous disease(CGD), lack phagocyte

oxidase complex superoxide production, increased susceptibility to infection and
altered inflammatory response to thioglycollate peritonitis
Dmd dystrophin, muscular hypertrophic skeletal muscles, fibre size variations with
dystrophy necrosis and regeneration

DXRib1 fortuitous transgenic cleft secondary palate, neonatal male lethality, suggested
insertion in locus model for human X-linked cleft secondary palate syndrome
Fmr1 fragile X mental Macroorchidism, learning deficits, hyperactivity and lack of
retardation syndrome 1 normal Fmr1 protein
homologue

G6pdx glucose-6-phosphate at ES cell level only, clones with undetectable levels of the
dehydrogenase enzyme are extremely sensitive to hydrogen peroxide and
diamide
Gata1 GATA-binding protein 1 male neonatal lethal, mid-gestation embryos pallid with arrest
of erythroid development

Page 5
 Different ref. format

Gjb1 gap junction protein from 3 months progressive demyelinating neuropathy, motor
connexin32 fibres more affected than sensory fibres, model for Charcot-
Marie-Tooth disease?
Gpc3 glypican 3

Grpr gastrin releasing no gross phenotypic abnormalities, but bombesin ineffective at

peptide receptor suppress glucose intake
Gyk glycerol kinase males normal at birth but exhibit growth retardation, altered fat
metabolism with profound hypoglycerolemia and elevated free
fatty acids, autonomous glucocorticoid synthesis and death by
3-4 days. Heterozygous females are healthy and biochemically
normal
Hprt hypoxanthine none unless Aprt also eliminated
phosphoribosyl-
transferase

Htr2c 5-hydroxytryptamine overweight because of abnormal feeding behaviour,

(serotonin) receptor 2C spontaneous death from seizures
Il2rg interleukin 2 receptor, similar phenotype to human XSCID, decrease in lymphocyte
gamma chain numbers but increase in monocytes, few T cells in young mice
and no natural killer cells

L1cam L1 cell adhesion smaller than wt animals, uncoordinated hind legs, hypoplasia
molecule of corticospinal tract, abnormal brain pathology, and impaired
exploratory behaviour
Maoa monoamine oxidase A pups had elevated serotonin levels, trembling, difficulty in
righting and fearfulness, adults had distinct behavioural
syndrome with enhanced aggression in males
Mpp1 murine p55

Ndph Norrie disease development of retrolental structures in vitreous body,

homologue disorganisation of retinal ganglion cell layer, occasional loss of
outer plexiform layer with resultant interchange of inner/outer
nuclear layer, absence of outer segments of photoreceptor cell
layer
Ocrl oculocerebrorenal no abnormal phenotype, with postulated compensation by the
syndrome of Lowe autosomal gene inositol polyphosphate 5-phosphatase
(Inpp5b) as explanation
Piga phosphatidylinositol wrinkled and scaly skin, death a few days after birth
glycan, class A
Plp myelin proteolipid assembly and maintenance of normal amounts of myelin,
protein(=DXNds2, progressive tract-specific axonopathy notes: (1) correction of
DXMit9, jimpy) natural mutant with wild type transgene not possible (2) over
expression has more severe clinical effects
Pou4f2 POU domain,class 4, selective loss of 70% of retinal ganglion cells, but other
transcription factor 2 neurons in the retina and brain essentially unaffected
Syn1 synapsin 1 no gross abnormalities, mossy fibre giant terminals reduced,
fewer synaptic vesicles, and presynaptic structures altered

Page 6
 Different ref. format

Syp synaptophysin indistinguishable from normal littermates, predendritic neurites

and axon outgrowth retarded in hippocampal neurons, with
delayed synapse formation

Timp tissue inhibitor of at ES cell level only, more invasive than normal cells
metalloproteinase
Wasp Wiskott-Aldrich decreased peripheral blood lymphocyte and platelet numbers,
syndrome protein chronic colitis

Xnp X-linked nuclear protein at cellular level, increased sensitivity to ionising radiation,
mitomycin C and methyl methanesulphonate

Page 7
 Different ref. format

OF X-LINKED GENES
References Posn.

J:39394:Ohshima et al. (1997) PNAS USA 94: 2540-2544 53.0

J:29456:Hein et al. (1995) Nature 377: 744-747; 12.5

J:29457:Ichiki et al. (1995) Nature 377: 748-750

J:42479:Lu et al. (1997) PNAS USA 94: 9366-9371; 29.5

J:44812:ForssPetter et al. (1997) J. Neurosci. Res. 50: 829-843

J:49647:Xu et al.(1998) Nature Genetics 20: 78-82 29.3

J:44242:Ohki-Hamazaki et al. (1997) Nature 390: 165-169

J:28967:Kerner et al. (1995) Immunity 3: 301-312; 51.0

Medline 97244169:Khan et al. (1997) Int. Immunol. 9: 395-405

Medline 95337793:Castigli et al. (1995) Int. Arch. Allergy 18.0

Immunol. 107: 37-39
J:24941:Bi et al. (1995) Nature Genetics 10: 119-121 30.5
J:43590:Wang et al. (1997) PNAS USA 94: 11563-11566 22.0

J:40673:van den Hurk et al (1997) Hum. Mol. Genet. 6: 851- 96.5

858
J:22868:Pollock et al. (1995) Nature Genetics 9: 202-209; 2.8
Medline 97169063:Morgenstern et al. (1997) J. Exp. Med. 185:
207-218
J:43164:Araki et al. (1997) Biochem. Biophys. Res. Comm. 32.0
238: 492-497

J:18214:Wilson et al. (1993) Cell Growth & Diff. 4: 67-76 ?

J:19220:Bakker et al. (1994) Cell 78: 23-33; 24.5

J:47489:Oostra and Hoogeveen et al. (1997) Annals of
Medicine 29: 563-567

Medline 96080156:Pandolfi et al. (1995) EMBO J. 14: 5209- 30.02

5215

J:36249:Fujiwara et al. (1996) PNAS USA 93: 12355-12358; 2.1

J:40321:Takahashi et al. (1997) J. Biol. Chem. 272: 12611-
12615

Page 8
 Different ref. format

Medline 98365842:Scherer et al. (1998) Glia 24: 8-20 38.0

J:47826:Li et al. (1998) Clin. Genet. 53: 165-170 ?

J:46897:Hampton et al. (1998) PNAS USA 95: 3188-3192 70.0

J:43449:Huq et al. (1997) Hum. Mol. Genet. 11: 1803-1809 33.0

J:15483:Hooper et al. (1987) Nature 326: 292-295; 17.0

J:15485:Kuehn et al. (1987) Nature 326: 295-298;
Medline 95134423:Nehls et al. (1994) Biotechniques 17: 770-
775;
J:41459:Tsuda et al.(1997) Genomics 42:413-421
J:24339:Tecott et al. (1995) Nature 374: 542-546 66.15

Medline 96422667:Leonard et al. (1995) Immunol. Rev. 148: 38.0

97-114;
Medline 96292426:Sugamura et al. (1996) Ann. Rev. Immunol.
14: 179-205;
J:31167:Ohbo et al. (1996) Blood 87: 956-967
J:43838:Dahme et al. (1997) Nature Genetics 17: 346-349; 29.51
J:47995:Fransen et al. (1998) Hum. Mol. Genet. 7: 999-1009

J:26232:Cases et al. (1995) Science 268: 1763-1766 5.2

IS 1059-1524:Kim et al. (1996) Mol. Biol. of the Cell 7: 999 30.48

J:30902:Berger et al. (1996) Hum. Mol. Genet. 5: 51-59 5.3

J:47884:Janne et al. (1998) J. Clin. Invest. 101: 2042-2053 ?

J:41746:Tarutani et al. (1997) PNAS USA 94: 7400-7405 67.0

J;31051:Griffiths et al. (1995) Brain Pathol. 5: 275-281; 56.0

J:38856:Klugmann et al. (1997) Neuron 18: 59-70;
Medline 98336162:Griffiths et al. (1998) Microsc. Res. Tech.
41: 344-358
J:32903:Gan et al. (1996) PNAS USA 93: 3920-3925;
J:33502:Erkman et al. (1996) Nature 381: 603-606
J:15701:Rosahl et al. (1993) Cell 75: 661-670; 6.2
J:30400:Takei et al. (1995) J. Cell Bio. 131: 1789-1800

Page 9
 Different ref. format

J:29085:Chin et al. (1995) PNAS USA 92: 9230-9234; 1.7

J:30488:Eshkind and Leube (1995) Cell Tissue Res. 282: 423-
433;
J:33035:McMahon et al. (1996) PNAS USA 93: 4760-4764
Medline 92348514:Alexander and Werb (1992) J. Cell Biol. 6.2
118: 727-739
J:48836:Snapper et al. (1998) Immunity 9: 81-91 2.1

J:39642:Essers et al. (1997) Cell 89: 195-204 43.8

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