Table 3.
Targeted Mutations at Mouse X-Linked Loci
| Symbol | Targeted gene | Phenotype details | References |
| Ags | α-galactosidase, mutated in Fabry disease # | phenotypically normal at 10 weeks, liver and kidney pathophysiology similar to human Fabry disease | Ohshima et al. (1997) |
| Agtr2 | angiotensin II receptor, type 2 | blood pressure increase, increased sensitivity to pressor action of angiotensin II, lowered body temperature, reduced exploratory behavior, anxiety-like behavior | Hein et al. (1995); Ichiki et al. (1995); Okuyama et al. (1999) |
| Abcd1 | ATP-binding cassette, subfamily D, member 1, mutated in adrenoleukodystrophy # | reduced β-oxidation of very long chain fatty acids (VLCFAs) with consequent elevation of saturated VLCFAs in total lipids of all tissues and cholesterol esters in adrenocortical cells, no neurological involvement seen in mice up to 6 months | ForssPetter et al. (1997); Lu et al. (1997) |
| Bgn | biglycan | skeletal phenotype marked by progressive lowering of bone mass, suggested model for role of ECM proteins in osteoporosis | Xu et al. (1998) |
| Brs3 | Bombesin receptor subtype-3 | mild obesity, hypertension, impaired glucose metabolism, reduced metabolic rate, increased feeding efficiency and subsequent hyperphagia | Ohki-Hamazaki et al. (1997) |
| Btk | Bruton agammaglobulinemia tyrosine kinase # | mild X-linked immunodeficiency, with additional compromise of B cell precursor expansion | Kerner et al. (1995); Khan et al. (1997) |
| CD40I | CD40 antigen ligand, mutated in hyper-IgM syndrome # | failure to undergo isotype switching to T-cell-dependent antigens, normal response to T-cell-independent antigens | Renshaw et al. (1994); Xu et al. (1994); Castigli et al. (1995) |
| Cf8 | coagulation factor VIII, mutated in hemophilia A # | <1% factor VIII clotting activity, significant bleeding after tail biopsy, which may be lethal, no spontaneous bleeding | Bi et al. (1995) |
| Cf9 | coagulation factor IX, mutated in hemophilia B # | absence of factor IX antigen in plasma, <5% factor IX clotting activity | Wang et al. (1997) |
| Cybb | subunit of NADPH-oxidase complex, mutated in chronic granulomatous disease # | chronic granulomatous disease, lack of phagocyte superoxide production, increased susceptibility to infection and altered inflammatory response to thioglycollate peritonitis | Pollock et al. (1995); Morgenstern et al. (1997) |
| Dmd | dystrophin, mutated in Duchenne muscular dystrophy # | hypertrophic skeletal muscles, fibre size variations with necrosis and regeneration | Araki et al. (1997) |
| Fmr1 | fragile X mental retardation syndrome 1 homolog # | macro-orchidism, learning deficits | Bakker et al. (1994); Oostra and Hoogeveen et al. (1997) |
| G6pdx | glucose-6-phosphate dehydrogenase | at ES cell level only, clones with undetectable levels of the enzyme are extremely sensitive to hydrogen peroxide and diamide | Pandolfi et al. (1995) |
| Gata1 | GATA-binding protein 1 | male neonatal lethal, mid-gestation embryos pallid with arrest of erythroid development | Pevny et al. (1991); Fujiwara et al. (1996); Takahashi et al. (1997) |
| Gjb1 | gap junction protein connexin32, mutated in X-linked CharcotMarie-Tooth disease # | from 3 months progressive demyelinating neuropathy, motor fibers more affected than sensory fibers | Scherer et al. (1998) |
| Gpc3 | glypican 3, mutated in, Simpson– Golabi–Behmel syndrome # | overgrowth, cystic kidneys | Li et al. (1998) |
| Grpr | gastrin releasing peptide receptor | no gross phenotypic abnormalities, loss of bombesin-induced feeding suppression | Hampton et al. (1998) |
| 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 | Huq et al. (1997) |
| Hprt | hypoxanthine phosphoribosyl transferase # | overgrooming in older mice, increased locomotor activity after amphetamine administration; self-injurious behavior only when inhibitor of Aprt also present (Wu and Melton 1993), model for Lesch–Nyhan disease | Hooper et al. (1987); Kuehn et al. (1987); Nehls et al. (1994); Tsuda et al. (1997) |
| Htr2c | 5-hydroxytryptamine (serotonin) receptor 2C | overweight because of abnormal feeding behavior, spontaneous death from seizures | Tecott et al. (1995) |
| II2rg | interleukin 2 receptor, γ chain, mutated in X-linked severe combined immunodeficiency # | similar phenotype to human XSCID, decrease in lymphocyte numbers but increase in monocytes, few T cells in young mice and no natural killer cells | Leonard et al. (1995); Ohbo et al. (1996); Sugamura et al. (1996) |
| L1cam | L1 cell adhesion molecule, mutated in CRASH syndrome # | smaller than wild type animals, uncoordinated hind legs, hypoplasia of corticospinal tract, abnormal brain pathology, and impaired exploratory behavior | Dahme et al. (1997); Fransen et al. (1998) |
| Maoa | monoamine oxidase a # | pups have elevated serotonin levels, trembling, difficulty in righting, fearfulness; adults have distinct behavioral syndrome with enhanced aggression in males | Cases et al. (1995) |
| Maob | monoamine oxidase b | increased reactivity to stress, increased levels of beta- phenylethylamine, resistance to neurodegenerative effects of MPTP toxin (which induces a Parkinson's- like condition) | Grimsby et al. (1997) |
| Mecp2 | methyl CpG binding protein 2, mutated in Rett syndrome # | chimeric embryos exhibit developmental defects with severity proportional to mutant cell contributions | Tate et al. (1996); Amir et al. (1999) |
| Ndph | Norrie disease homolog # | development of retrolental structures in vitreous body, disorganization 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 | Berger et al. (1996) |
| Ocrl | oculocerebrorenal syndrome of Lowe # | no abnormal phenotype, with postulated compensation by the autosomal gene inositol polyphosphate 5-phosphatase (lnpp5b) as explanation | Janne et al. (1998) |
| Piga | phosphatidylinositol glycan, class A | wrinkled and scaly skin, death a few days after birth | Tarutani et al. (1997) |
| Plp | myelin proteolipid protein, mutated in Pelizaeus– Merzbacher disease # | no gross effect, assembly and maintenance of normal amounts of myelin, progressive tract-specific axonopathy | Boison and Stoffel (1994);Griffiths et al. (1995); Klugmann et al. (1997); Griffiths et al. (1998) |
| Pou3f4 | Pou domain, class 3, transcription factor 4, mutated in DFN3 # | vertical head bobbing and hearing loss, dysplastic bony compartment of the inner ear | Minowa et al. (1999); Phippard et al. (1999) |
| Pou4f2 | POU domain, class 4, transcription factor 2 | selective loss of 70% of retinal ganglion cells, other neurons in the retina and brain essentially unaffected | Erkman et al. (1996); Gan et al. (1996) |
| Rep1 | Rab escort protein 1, mutated in choroideremia # | embryonic male lethal; heterozygous females and chimeras have a variable number of photoreceptor cells | van den Hurk et al. (1997) |
| Syn1 | synapsin 2 | no gross abnormalities, mossy fibre giant terminals reduced, fewer synaptic vesicles, presynaptic structures altered | Rosahl et al. (1993); Takei et al (1995) |
| Syp | synaptophysin | indistinguishable from normal littermates, predendritic neurites and axon outgrowth retarded in hippocampal neurons, with delayed synapse formation; homozygotes die prior to 10.5 dpc | Chin et al. (1995); Erhkind and Leube (1995); Arrandale et al. (1996); McMahon et al. (1996) |
| Timp | tissue inhibitor of metalloproteinase | no effect on steroidogenesis, reduced ovarian TIMP2 and TIMP3, at ES cell level only, more invasive than normal cells | Alexander and Werb (1992); Nothnick et al. (1997) |
| Wasp | Wiskott–Aldrich syndrome protein # | decreased peripheral blood lymphocyte and platelet numbers, chronic colitis | Snapper et al. (1998) |
| Xist | inactive X specific transcripts | mutant males unaffected, females inheriting mutant paternal X chromosome severely retarded and die in utero | Penny et al. (1996); Marahens et al. (1997) |
| Xnp | X-linked nuclear protein, mutated in α-thalassemia mental retardation syndrome # | at cellular level, increased sensitivity to ionizing radiation, mitomycin C, and MMS | Essers et al. (1997) |
| Zfx | X-linked zinc finger protein | male and female mutants smaller, with lower viability and fewer germ cells, hemizygotes had reduced sperm count and homozygotes a reduced number of oocytes | Luoh et al. (1997) |
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Genes associated with known human disease are indicated by a pound sign (#) after the gene name; where the disease has a different name, it is given in the same column. Targeted genes are given in alphabetical order of gene symbol. Note that a meeting abstract also mentions the targeting of the mouse p55 gene Mpp1 (A.C. Kim, C.D. Southgate, B.J. Mitchell, and A.H. Chistiti, unpubl.), but as no details of the resulting phenotype are provided this locus is not included in the table.
